Radical lupus treatment uses CAR T-cell therapy developed for cancer – New Scientist

Five people with the autoimmune condition lupus are now in remission after receiving a version of CAR-T therapy, which was originally developed for cancer

By Clare Wilson

Illustration of a CAR-T cell

CHRISTOPH BURGSTEDT/SCIENCE PHOTO LIBRARY

A high-tech cell therapy used to treat cancer has been repurposed as a treatment for lupus, an autoimmune condition that can cause joint, kidney and heart damage.

CAR T-cell therapy has put all five people with lupus treated so far into remission. The participants have been followed up for an average of 8 months, with the first person treated 17 months ago. Thats kind of unheard of, says Chris Wincup at Kings College London, who wasnt involved in the study. This is incredibly exciting.

But it is too soon to know how long the remissions will last, says Georg Schett at the University of Erlangen-Nuremberg in Germany, who was part of the study team.

CAR T-cells were developed to treat blood cancers that arise when B cells, a type of immune cell that normally makes antibodies, start multiplying out of control.

The approach requires taking a sample of immune cells from a persons blood, genetically altering them in the lab so they attack B cells and then infusing them back into the individuals blood. It seems to put 4 out of 10 people with these kinds of cancers into remission.

Lupus, also called systemic lupus erythematosus, is caused by the immune system mistakenly reacting against peoples own DNA. This is driven by B cells making antibodies against DNA released from dying cells.

It is currently treated with medicines that suppress the immune system or, in more severe cases, with drugs that kill B cells. But the treatments cant kill all the B cells, and if the disease flares up badly, some people develop kidney failure and inflammation of their heart and brain.

Schett and his team wondered whether using CAR T-cells to hunt down all the B cells would be more effective. Within three months of receiving the treatment, all five participants were in remission, without needing to take any other medicines to control their symptoms.

The CAR T-cells were barely detectable after one month, and after three and a half months, the volunteers B cells started to return, having been produced by stem cells in bone marrow. These new B cells didnt react against the DNA.

We dont know what normally causes B cells to start reacting against DNA in people with lupus, so it is possible that some kind of trigger may start the process happening again, says Wincup.

The achievement means CAR T-cells may also be useful against other autoimmune diseases that are driven by antibodies, such as multiple sclerosis (MS), in which the immune system attacks nerves, says Schett.

Another radical treatment for MS involves rebooting the immune system by destroying it with chemotherapy. By comparison, CAR T-cells would be less invasive and more tolerable, he says.

But it is too soon to know how effective CAR T-cells will be for autoimmune conditions, says Wincup. This is a small number of patients, so we dont know if this is going to be the result for everyone.

When used in cancer, CAR T-cells are expensive to create for each person, so they may only be used for autoimmune conditions in people with severe disease when no other treatments are available, he says.

Journal reference: Nature Medicine , DOI: 10.1038/s41591-022-02017-5

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Radical lupus treatment uses CAR T-cell therapy developed for cancer - New Scientist

Kite’s CAR T-cell Therapy Yescarta First in Europe to Receive Positive CHMP Opinion for Use in Second-line Diffuse Large B-cell Lymphoma and…

Positive Opinion Based on Landmark ZUMA-7 Study in Which 41% of Patients Demonstrated Event-Free Survival at Two Years versus 16% for Standard of Care -

SANTA MONICA, Calif.--(BUSINESS WIRE)-- Kite, a Gilead Company (Nasdaq: GILD), today announces that the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for Yescarta (axicabtagene ciloleucel) for adult patients with diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) that relapses within 12 months from completion of, or is refractory to, first-line chemoimmunotherapy. If approved, Yescarta will be the first Chimeric Antigen Receptor (CAR) T-cell therapy approved for patients in Europe who do not respond to first-line treatment. Although 60% of newly diagnosed LBCL patients will respond to their initial treatment, 40% will relapse or will not respond and need 2nd line treatment.

At Kite, we are committed to bringing the curative potential of cell therapy to the world, and changing the way cancer is treated, said Christi Shaw, CEO, Kite. Todays positive CHMP opinion brings us a step closer to utilizing cell therapy earlier in the treatment journey, potentially transforming the standard of care for the most common and aggressive form of non-Hodgkin lymphoma.

The European Commission will review the CHMP opinion, and a final decision on the marketing authorization is expected in the coming months.

For people with DLBCL and HGBL who do not respond to first-line treatment or have an early relapse, outcomes are often poor and there are limited curative treatment options for these patients, said Marie Jos Kersten, Professor of Hematology at Amsterdam University Medical Centers, Amsterdam. If approved, axicabtagene ciloleucel may offer a new standard of care for patients with relapsed or refractory DLBCL and HGBL. Importantly, in a randomized trial of axicabtagene ciloleucel versus the current standard of care, quality of life also showed greater improvement in the experimental arm.

The positive opinion for Yescarta is based on the primary results of the landmark Phase 3 ZUMA-7 study, the largest and longest trial of a CAR T-cell therapy versus standard of care (SOC) in second-line LBCL. Results demonstrated that at a median follow-up of two years, Yescarta-treated patients had a four-fold greater improvement in the primary endpoint of event-free survival (EFS; hazard ratio 0.40; 95% CI: 0.31-0.51, P<0.001) over the current SOC (8.3 months v 2.0 months). Additionally, Yescarta demonstrated a 2.5 fold increase in patients who were alive at two years without disease progression or need for additional cancer treatment vs SOC (41% v 16%). Improvements in EFS with Yescarta were consistent across key patient subgroups, including elderly patients (HR: 0.28 [95% CI: 0.16-0.46]), primary refractory patients (HR: 0.43 [95% CI: 0.32- 0.57]), high-grade B cell lymphoma including double-hit and triple-hit lymphoma patients (HGBL; HR: 0.28 [95% CI: 0.14-0.59]), and double expressor lymphoma patients (HR: 0.42 [95% CI: 0.27-0.67]).

In a separate, secondary analysis of Patient-Reported Outcomes (PROs) published in Blood patients receiving Yescarta and eligible for the PROs portion of the study (n=165) showed statistically significant improvements in Quality of Life (QoL) at Day 100 compared with those who received SOC (n=131), using a pre-specified analysis for three PRO-domains (EORTC QLQ-C30 Physical Functioning, EORTC QLQ-C30 Global Health Status/QOL, and EQ-5D-5L visual analog scale [VAS]). There was also a trend toward faster recovery to baseline QoL in the Yescarta arm versus SOC.

In the ZUMA-7 trial, Yescarta had a manageable safety profile that was consistent with previous studies. Among the 170 Yescarta-treated patients evaluable for safety, Grade 3 cytokine release syndrome (CRS) and neurologic events were observed in 6% and 21% of patients, respectively. No Grade 5 CRS or neurologic events occurred. In the SOC arm, 83% of patients had high-grade events, mostly cytopenias (low blood counts).

About ZUMA-7

ZUMA-7 is an ongoing, randomized, open-label, global, multicenter (US, Australia, Canada, Europe, Israel) Phase 3 study of 359 patients at 77 centers, evaluating the safety and efficacy of a single-infusion of Yescarta versus current SOC for second-line therapy (platinum-based salvage combination chemotherapy regimen followed by high-dose chemotherapy and autologous stem cell transplant in those who respond to salvage chemotherapy) in adult patients with relapsed or refractory LBCL within 12 months of first-line therapy. The primary endpoint is event free survival (EFS) as determined by blinded central review, and defined as the time from randomization to the earliest date of disease progression per Lugano Classification, commencement of new lymphoma therapy, or death from any cause. Key secondary endpoints include objective response rate (ORR) and overall survival (OS). Additional secondary endpoints include patient reported outcomes (PROs) and safety.

About Yescarta

Yescarta was first approved in Europe in 2018 and is currently indicated for three types of blood cancer: Diffuse Large B-Cell Lymphoma (DLBCL); Primary Mediastinal Large B-Cell Lymphoma (PMBCL); and Follicular Lymphoma (FL). For the full European Prescribing Information, please visit: https://www.ema.europa.eu/en/medicines/human/EPAR/yescarta

Please see full US Prescribing Information, including BOXED WARNING and Medication Guide.

YESCARTA is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:

U.S. IMPORTANT SAFETY INFORMATION

BOXED WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITIES

CYTOKINE RELEASE SYNDROME (CRS)

CRS, including fatal or life-threatening reactions, occurred. CRS occurred in 90% (379/422) of patients with non-Hodgkin lymphoma (NHL), including Grade 3 in 9%. CRS occurred in 93% (256/276) of patients with large B-cell lymphoma (LBCL), including Grade 3 in 9%. Among patients with LBCL who died after receiving YESCARTA, 4 had ongoing CRS events at the time of death. For patients with LBCL in ZUMA-1, the median time to onset of CRS was 2 days following infusion (range: 1-12 days) and the median duration was 7 days (range: 2-58 days). For patients with LBCL in ZUMA-7, the median time to onset of CRS was 3 days following infusion (range: 1-10 days) and the median duration was 7 days (range: 2-43 days). CRS occurred in 84% (123/146) of patients with indolent non-Hodgkin lymphoma (iNHL) in ZUMA-5, including Grade 3 in 8%. Among patients with iNHL who died after receiving YESCARTA, 1 patient had an ongoing CRS event at the time of death. The median time to onset of CRS was 4 days (range: 1-20 days) and the median duration was 6 days (range: 1-27 days) for patients with iNHL.

Key manifestations of CRS ( 10%) in all patients combined included fever (85%), hypotension (40%), tachycardia (32%), chills (22%), hypoxia (20%), headache (15%), and fatigue (12%). Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), renal insufficiency, cardiac failure, respiratory failure, cardiac arrest, capillary leak syndrome, multi-organ failure, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome.

The impact of tocilizumab and/or corticosteroids on the incidence and severity of CRS was assessed in 2 subsequent cohorts of LBCL patients in ZUMA-1. Among patients who received tocilizumab and/or corticosteroids for ongoing Grade 1 events, CRS occurred in 93% (38/41), including 2% (1/41) with Grade 3 CRS; no patients experienced a Grade 4 or 5 event. The median time to onset of CRS was 2 days (range: 1-8 days) and the median duration of CRS was 7 days (range: 2-16 days). Prophylactic treatment with corticosteroids was administered to a cohort of 39 patients for 3 days beginning on the day of infusion of YESCARTA. Thirty-one of the 39 patients (79%) developed CRS and were managed with tocilizumab and/or therapeutic doses of corticosteroids with no patients developing Grade 3 CRS. The median time to onset of CRS was 5 days (range: 1-15 days) and the median duration of CRS was 4 days (range: 1-10 days). Although there is no known mechanistic explanation, consider the risk and benefits of prophylactic corticosteroids in the context of pre-existing comorbidities for the individual patient and the potential for the risk of Grade 4 and prolonged neurologic toxicities.

Ensure that 2 doses of tocilizumab are available prior to YESCARTA infusion. Monitor patients for signs and symptoms of CRS at least daily for 7 days at the certified healthcare facility, and for 4 weeks thereafter. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated.

NEUROLOGIC TOXICITIES

Neurologic toxicities (including immune effector cell-associated neurotoxicity syndrome) that were fatal or life-threatening occurred. Neurologic toxicities occurred in 78% (330/422) of all patients with NHL receiving YESCARTA, including Grade 3 in 25%. Neurologic toxicities occurred in 87% (94/108) of patients with LBCL in ZUMA-1, including Grade 3 in 31% and in 74% (124/168) of patients in ZUMA-7 including Grade 3 in 25%. The median time to onset was 4 days (range: 1-43 days) and the median duration was 17 days for patients with LBCL in ZUMA-1. The median time to onset for neurologic toxicity was 5 days (range:1- 133 days) and the median duration was 15 days in patients with LBCL in ZUMA-7. Neurologic toxicities occurred in 77% (112/146) of patients with iNHL, including Grade 3 in 21%. The median time to onset was 6 days (range: 1-79 days) and the median duration was 16 days. Ninety-eight percent of all neurologic toxicities in patients with LBCL and 99% of all neurologic toxicities in patients with iNHL occurred within the first 8 weeks of YESCARTA infusion. Neurologic toxicities occurred within the first 7 days of infusion for 87% of affected patients with LBCL and 74% of affected patients with iNHL.

The most common neurologic toxicities ( 10%) in all patients combined included encephalopathy (50%), headache (43%), tremor (29%), dizziness (21%), aphasia (17%), delirium (15%), and insomnia (10%). Prolonged encephalopathy lasting up to 173 days was noted. Serious events, including aphasia, leukoencephalopathy, dysarthria, lethargy, and seizures occurred. Fatal and serious cases of cerebral edema and encephalopathy, including late-onset encephalopathy, have occurred.

The impact of tocilizumab and/or corticosteroids on the incidence and severity of neurologic toxicities was assessed in 2 subsequent cohorts of LBCL patients in ZUMA-1. Among patients who received corticosteroids at the onset of Grade 1 toxicities, neurologic toxicities occurred in 78% (32/41), and 20% (8/41) had Grade 3 neurologic toxicities; no patients experienced a Grade 4 or 5 event. The median time to onset of neurologic toxicities was 6 days (range: 1-93 days) with a median duration of 8 days (range: 1-144 days). Prophylactic treatment with corticosteroids was administered to a cohort of 39 patients for 3 days beginning on the day of infusion of YESCARTA. Of those patients, 85% (33/39) developed neurologic toxicities, 8% (3/39) developed Grade 3, and 5% (2/39) developed Grade 4 neurologic toxicities. The median time to onset of neurologic toxicities was 6 days (range: 1-274 days) with a median duration of 12 days (range: 1-107 days). Prophylactic corticosteroids for management of CRS and neurologic toxicities may result in a higher grade of neurologic toxicities or prolongation of neurologic toxicities, delay the onset of and decrease the duration of CRS.

Monitor patients for signs and symptoms of neurologic toxicities at least daily for 7 days at the certified healthcare facility, and for 4 weeks thereafter, and treat promptly.

REMS

Because of the risk of CRS and neurologic toxicities, YESCARTA is available only through a restricted program called the YESCARTA and TECARTUS REMS Program which requires that: Healthcare facilities that dispense and administer YESCARTA must be enrolled and comply with the REMS requirements and must have on-site, immediate access to a minimum of 2 doses of tocilizumab for each patient for infusion within 2 hours after YESCARTA infusion, if needed for treatment of CRS. Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer YESCARTA are trained in the management of CRS and neurologic toxicities. Further information is available at http://www.YescartaTecartusREMS.com or 1-844-454-KITE (5483).

HYPERSENSITIVITY REACTIONS

Allergic reactions, including serious hypersensitivity reactions or anaphylaxis, may occur with the infusion of YESCARTA.

SERIOUS INFECTIONS

Severe or life-threatening infections occurred. Infections (all grades) occurred in 45% of patients with NHL; Grade 3 infections occurred in 17% of patients, including Grade 3 infections with an unspecified pathogen in 12%, bacterial infections in 5%, viral infections in 3%, and fungal infections in 1%. YESCARTA should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after infusion and treat appropriately. Administer prophylactic antimicrobials according to local guidelines.

Febrile neutropenia was observed in 36% of all patients with NHL and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids, and other supportive care as medically indicated.

In immunosuppressed patients, including those who have received YESCARTA, life-threatening and fatal opportunistic infections including disseminated fungal infections (e.g., candida sepsis and aspergillus infections) and viral reactivation (e.g., human herpes virus-6 [HHV-6] encephalitis and JC virus progressive multifocal leukoencephalopathy [PML]) have been reported. The possibility of HHV-6 encephalitis and PML should be considered in immunosuppressed patients with neurologic events and appropriate diagnostic evaluations should be performed.

Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells, including YESCARTA. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing.

PROLONGED CYTOPENIAS

Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and YESCARTA infusion. Grade 3 cytopenias not resolved by Day 30 following YESCARTA infusion occurred in 39% of all patients with NHL and included neutropenia (33%), thrombocytopenia (13%), and anemia (8%). Monitor blood counts after infusion.

HYPOGAMMAGLOBULINEMIA

B-cell aplasia and hypogammaglobulinemia can occur. Hypogammaglobulinemia was reported as an adverse reaction in 14% of all patients with NHL. Monitor immunoglobulin levels after treatment and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement. The safety of immunization with live viral vaccines during or following YESCARTA treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during YESCARTA treatment, and until immune recovery following treatment.

SECONDARY MALIGNANCIES

Secondary malignancies may develop. Monitor life-long for secondary malignancies. In the event that one occurs, contact Kite at 1-844-454-KITE (5483) to obtain instructions on patient samples to collect for testing.

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES

Due to the potential for neurologic events, including altered mental status or seizures, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following YESCARTA infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

ADVERSE REACTIONS

The most common non-laboratory adverse reactions (incidence 20%) in patients with LBCL in ZUMA-7 included fever, CRS, fatigue, hypotension, encephalopathy, tachycardia, diarrhea, headache, musculoskeletal pain, nausea, febrile neutropenia, chills, cough, infection with an unspecified pathogen, dizziness, tremor, decreased appetite, edema, hypoxia, abdominal pain, aphasia, constipation, and vomiting.

The most common adverse reactions (incidence 20%) in patients with LBCL in ZUMA-1 included CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections with an unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias.

The most common non-laboratory adverse reactions (incidence 20%) in patients with iNHL in ZUMA-5 included fever, CRS, hypotension, encephalopathy, fatigue, headache, infections with an unspecified, tachycardia, febrile neutropenia, musculoskeletal pain, nausea, tremor, chills, diarrhea, constipation, decreased appetite, cough, vomiting, hypoxia, arrhythmia, and dizziness.

About Kite

Kite, a Gilead Company, is a global biopharmaceutical company based in Santa Monica, California, with manufacturing operations in North America and Europe. Kites singular focus is cell therapy to treat and potentially cure cancer. As the cell therapy leader, Kite has more approved CAR T indications to help more patients than any other company. For more information on Kite, please visit http://www.kitepharma.com. Follow Kite on social media on Twitter (@KitePharma) and LinkedIn.

About Gilead Sciences

Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California.

Forward-Looking Statements

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the ability of Gilead and Kite to initiate, progress or complete clinical trials within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing and additional clinical trials, including those involving Yescarta; uncertainties relating to regulatory applications and related filing and approval timelines, including the risk that the European Commission may not grant marketing authorization for Yescarta for use in second-line DLBCL and HGBL in a timely manner or at all; the risk that any regulatory approvals, if granted, may be subject to significant limitations on use; the risk that physicians may not see the benefits of prescribing Yescarta for the treatment of LBCL; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and other factors are described in detail in Gileads Quarterly Report on Form 10-Q for the quarter ended June 30, 2022 as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead and Kite, and Gilead and Kite assume no obligation and disclaim any intent to update any such forward-looking statements.

U.S. Prescribing Information for Yescarta including BOXED WARNING, is available at http://www.kitepharma.com and http://www.gilead.com .

Kite, the Kite logo, Yescarta and GILEAD are trademarks of Gilead Sciences, Inc. or its related companies .

View source version on businesswire.com: https://www.businesswire.com/news/home/20220916005209/en/

Jacquie Ross, Investors investor_relations@gilead.com

Anna Padula, Media apadula@kitepharma.com

Source: Gilead Sciences, Inc.

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Kite's CAR T-cell Therapy Yescarta First in Europe to Receive Positive CHMP Opinion for Use in Second-line Diffuse Large B-cell Lymphoma and...

The Biggest CGT Breakthroughs Through the Eyes of Our 2022 Power List – The Medicine Maker

The relatively short history of cell and gene therapy is not lacking in dramatic moments. A previous outlier, this vibrant field now represents the next great hope and so, when roadblocks to progress are removed or even lowered, theres reason to celebrate. Here, seven members of The Medicine Maker Power List 2022, reflect on the most impactful cell and gene milestones.

There have been many significant breakthroughs in cell and gene therapy over the past few years. Specifically in gene-modified cell therapy, the CAR T story is remarkable. Over the past several years, multiple autologous CAR T therapies have been successfully translated from bench to bedside and received marketing authorization as potentially curative therapies for patients with recalcitrant cancer indications: Kymriah and Yescarta for treating r/r/ ALL, MCL, and LBCL, and Abecma for treating r/r multiple myeloma.

Equally impressive in gene therapy, Zolgensma, an AAVSMN1 gene replacement product, has been developed for use as a one-time gene replacement treatment for infants with spinal muscular atrophy (SMA). The 15 year follow-up study these tiny patients are enrolled in after treatment will inform us on the long-term safety and efficacy of gene replacement therapy.

These products have been translated by academia and SMEs and partnered for advanced development with pharma to achieve both medical and commercial success.

The biggest breakthrough is our increasing ability to edit genes with a growing number of new classes of gene editing tools. This advance has led to the boom of CAR T products and is opening the path to cell engineering and in vivo gene therapy.

In parallel, we are seeing an evolution from viral delivery to alternatives with growing payload capacity. This will, as we are already seeing, lead to cures in diseases where that was unthinkable before!

Cell and gene therapies are at the forefront of innovation and transforming how we treat and potentially cure certain diseases. Cell and gene therapies(CGTs) have the potential to treat severe diseases, such as cancer, as well as rare diseases. Several such therapies are now on the market, including a treatment for an inherited retinal disease that causes blindness. That particular CGT represents an important medical milestone because it was the first curative gene therapy approved for use. Personally, I was excited and humbled at the same time to have been the Global Head bringing this transformational therapy to patients around the world. Many other CGTs are now in development and hopefully will lead to an expansion of the still-limited treatment options available to many patients and transform the clinical paradigm.

An important breakthrough? The demonstration that gain-of-function genetically weaponized somatic cells are potent pharmaceuticals in their own right: living synthetic therapeutics (LSTs).Case in point, after a quarter century of work with TILs and LAKs struggling to meet utilitarian endpoints, enter gain-of-function CAR engineering, and thus history is made.The same paradigm of cell gain-of-function genetic enhancement can readily be applied to alternate somatic cell platforms think MSCs and iPSCs with a limitless potential to improve clinical outcomes for acute and chronic ailments.

Id like to emphasize three milestones. First, the commercialization of gene therapies in general. The efficacy and safety have improved a lot since the 1990s.

Secondly, the explosion of immunotherapies. Onco-hematology has become a major opportunity for patients with otherwise lethal blood cancers.

Finally, the advances in gene editing technologies. These have opened the door to new therapies which we would have considered utterly incredible a few years ago.

The recent approval for Yescarta in second-line (2L) relapsed/refractory large B-cell lymphoma (LBCL) means that an order-of-magnitude more patients just became eligible for potentially curative therapies. One recent industry insight from Celltelligence suggested that moving from 3L to 2L will potentially double the targetable population in diffuse LBCL alone for CAR T cell therapy. As cell therapies move up the treatment paradigm and cell-based therapeutics are eventually approved to treat a range of cancers, the spotlight will turn (again) to manufacturing capacity. At Cellares, our belief is that high-throughput, end-to-end automation is set to revolutionize cell therapy manufacturing, allowing us to deliver more doses at lower cost to meet the demand. Its a truly exciting time for our industry!

The success of the CAR T cell therapy approach and how it has led to cures for childhood leukemias and lymphomas is an amazing story. Thanks to these incredible advances, kids who would no longer be here today are now effectively cured, and are going to live long, relatively healthy lives without suffering the long-term side effects of traditional chemotherapy and radiation. By allowing investigators to be highly creative in developing this approach, a fascinating new treatment process was developed, for both autologous and allogeneic CAR T cell therapies. Now, an entire industry has been born from utilizing patients and donors stem cells and a modified version of the AIDS virus to cure leukemia. This is truly a mind-blowing advancement that combines so many complex processes and biologics and really showcases the power of creative investigators to come up with amazing new treatment solutions.

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The Biggest CGT Breakthroughs Through the Eyes of Our 2022 Power List - The Medicine Maker

Cell Culture Media Market worth $10.3 billion by 2026 – Exclusive Report by MarketsandMarkets – GlobeNewswire

Chicago, Sept. 13, 2022 (GLOBE NEWSWIRE) -- According to the new market research report "Cell Culture Media Market by Type(Serum-free (CHO, BHK, Vero Cell), Stem Cell, Chemically Defined, Classical, Specialty), Application(Biopharmaceutical (mAbs, Vaccine), Diagnostics, Tissue Engineering), End User(Pharma, Biotech) - Global Forecast to 2026", is projected to USD 10.3 billion by 2026 from USD 4.9 billion in 2021, at a CAGR of 16.0 % between 2021 and 2026.

Browse in-depth TOC on "Cell Culture Media Market" 314 - Tables 41 - Figures 303 - Pages

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The growth of this market is majorly driven by the rising R&D spending in pharmaceutical companies, emerging cell culture technologies for cell-based vaccines, increasing demand for monoclonal antibodies, growth in stem cell research, the launch of new cell culture media by market players, and the growing focus on personalized medicine. On the other hand, expensive cell biology research products and ethical concerns regarding cell biology research are expected to hinder the growth of this market.

Based on type, the cell culture media market is segmented intoserum-free media, classical media & salts, stem cell culture media, specialty media, chemically defined media, and other cell culture media. In 2020, the serum-free media segment accounted for the largest share of the market. This can be attributed to the advantages of serum-free media over other types of media, including consistent performance, increased growth & productivity, better control over physiological responsiveness, and reduced risk of contamination by serum-borne adventitious agents in cell culture.

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Based on application, the cell culture media market is categorized into biopharmaceutical production, diagnostics, drug discovery & development, tissue engineering & regenerative medicine, and other applications. The biopharmaceutical production segment is further divided into monoclonal antibody production, vaccine production, and other therapeutic protein production. The tissue engineering & regenerative medicine segment is further divided into cell & gene therapy and other tissue engineering & regenerative medicine applications.The biopharmaceutical production segment is estimated to grow at the highest rate during the forecast period. The high growth of this segment is attributed to the commercial expansion of major pharmaceutical and biotechnology companies, the increasing demand for mAbs, and the growing regulatory approvals for the production of cell culture-based vaccines.

Based on end user, the cell culture media market is segmented into pharmaceutical & biotechnology companies, hospitals & diagnostic laboratories, research & academic institutes, and other end users (such as cell banks, CDMOs, and CROs). In 2020, the pharmaceutical & biotechnology companies segment accounted for the largest share of the market. This end-user segment is also estimated to grow at the highest growth rate during the forecast period.

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Geographical Growth Scenario:

The global cell culture media market has been segmented into North America, Europe, the Asia Pacific, Latin America, and the Middle East and Africa. The Asia Pacific market is estimated to register the highest CAGR during the forecast period. The growing geriatric population, favorable regulatory guidelines, government support for cell culture-based vaccine production, low manufacturing costs, and the growing focus of global market players on emerging Asian economies are the major factors contributing to the growth of the market in the Asia Pacific.

Key Players:

Key players in the cell culture media market include Thermo Fisher Scientific, Inc. (US), Merck KGaA (Germany), Danaher Corporation (US), and Sartorius AG (Germany), Corning Incorporated (US).

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Cell Expansion Market by Product (Reagent, Media, Flow Cytometer, Centrifuge, Bioreactor), Cell Type (Human, Animal), Application (Regenerative Medicine & Stem Cell Research, Cancer & Cell-based Research), End-User, and Region - Global Forecast to 2025

Cell Culture Market by Product (Consumables (Media, Serum, Reagent, Vessels), Equipment (Bioreactor, Centrifuge, Incubator)), Application (Vaccines, mAbs, Diagnostics, Tissue Engineering), End User (Pharma, Biotech, Hospital) - Global Forecast to 2026

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Cell Culture Media Market worth $10.3 billion by 2026 - Exclusive Report by MarketsandMarkets - GlobeNewswire

The five hottest private biotech companies in India – Labiotech.eu

India is brimming with biotech companies and a young and skilled workforce. Heres a quick glance at the private healthcare biotechs in India that captured investors imaginations in the last couple of years.

India has historically been known for its large IT, pharmaceutical and vaccine manufacturing sectors, but is also a force to be reckoned with in the global biotechnology market. The nation boasts around 5,000 biotech companies, with more than 4,000 being startups. This startup count is expected to reach 10,000 by 2024.

With a huge population of young and skilled workers, India has many ingredients for expanding the number of its biotech companies in the coming years. Add to this a large patient pool for lifestyle-related diseases such as type 2 diabetes, and there is a large potential for generating innovations in healthcare.

Weve assembled a shortlist of the hottest private biotech companies in India by checking whos raised impressive cash in the last few years. These companies are carrying out innovative healthcare research and are primarily based in Mumbai and Bengaluru.

Founded: 2014

Headquarters: Bengaluru, India and Saratoga, U.S.

Bugworks has multiple sites in the U.S. and Australia with a research and development base in India. The firm specializes in the development of antibiotics that could address the growing crisis of antimicrobial resistance.

Bugworks lead candidate antibiotic blocks the replication machinery in invading bacteria. In addition, the drug is designed to bypass normal resistance mechanisms in bacteria, which could make it harder for strains to become resistant to the treatment.

The company is testing its antibiotic in phase 1 trials for the treatment of multi-drug resistant infections in collaboration with the nonprofit initiatives CARB-X and the Global Antibiotic Research and Development Partnership (GARDP).

Bugworks is financing its antibiotics research with a $18 million Series B1 round closed in February 2022. In addition, Bugworks will use the proceeds to fund the preclinical development of a dual-acting drug to treat cancer.

Founded: 2012

Headquarters: Mumbai

Epigeneres Biotech hit the headlines in January 2022 with a $6 million Series B funding round. The Indian biotech company is using the cash to develop a wide range of different technologies in its arsenal, including cancer tests, nanotechnology-based medicines and nutraceuticals.

Cancer detection is Epigeneres most recent pursuit. In 2021, the firm teamed up with the Singaporean company Tzar Labs to develop cancer diagnostics that screen for telltale RNA molecules from tumors at early stages of disease. Epigeneres is poised to launch a screening service in India based on the technology.

Epigeneres also has nucleic acid drugs in development for the treatment of conditions ranging from infertility to renal failure to autoimmune diseases. The firm uses a form of nanotechnology to boost the delivery of the drugs to the target cells.

In addition, Epigeneres is working on small molecule drugs that can increase the population of stem cells in the body in a regenerative medicine setting.

Founded: 2016

Headquarters: Bengaluru

In August 2022, Eyestem caught the eye of investors in a $6.4 million Series A round. The Indian biotech startup is working on cell therapies for eye disorders, with a flagship therapy in the pipeline for the treatment of dry age-related macular degeneration (dry AMD).

There is currently no treatment for dry AMD. In patients with the condition, the eye accumulates cellular debris, which causes destructive inflammation in the retina. This leads to a loss of retinal pigment epithelium, the layer of cells that support the photosensitive cells we need to see.

Eyestem is developing an off-the-shelf stem cell therapy to replace lost retinal pigment epithelium. The biotech has earmarked money from its recent Series A round for preparing its cell therapy for early-stage clinical testing.

Founded: 2019

Headquarters: Bengaluru

Immuneel Therapeutics is making waves in the field of autologous CAR-T cell therapy, where a patients immune T cells are removed, engineered in the lab to kill blood cancer cells, and reinfused into the patient. There are CAR-T therapies already available, but these complex, expensive therapies are currently limited to only the wealthiest countries.

Immuneels mission is to develop CAR-T therapies that are accessible and affordable in India. To support this push, the company raised $15 million in June 2022 in a Series A round.

The therapies in Immuneels pipeline are targeted to various types of blood cancer in children and adult patients. As the Indian biotech closed its Series A round, Immuneel kicked off a phase 2 trial of a CAR-T therapy in what it claims is the first industry-sponsored CAR-T trial in India.

Founded: 2013

Headquarters: Bengaluru and Wilmington, U.S.

MedGenome has sites around the globe, with a large part of its operations and genetic testing situated in, and targeted to, India.

The company carries out genomics-focused research and diagnostics services for biopharma clients that can help in the development of drugs tackling cancer, diabetes, eye conditions and cardiovascular diseases. To provide a rich dataset, the company works with more than 500 hospitals in India.

MedGenome raised one of the Asia-Pacific regions biggest biotech investments in August 2022 a $50 million round led by Novo Holdings. The funds will be used to increase access to genetic testing in emerging markets, which have lagged behind the wealthier parts of the world.

MedGenome also aims to collect genetic data from a wide range of populations in Asia, which could provide a treasure trove of clinical insights for genes related to disease. In keeping with this aim, the company is a founding member of the initiative GenomeAsia 100K, which will analyze the genomes of 100,000 people from a range of Asian populations to speed up the development of precision medicine in this part of the world.

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The five hottest private biotech companies in India - Labiotech.eu

A history of blood cancer treatment – – pharmaphorum

Despite being one of the most common forms of cancer, awareness of blood cancer pales in comparison to other types of the disease. In fact, according to Blood Cancer UK research, more than half of UK adults cannot name a single symptom of blood cancer.

Over the past two centuries, researchers have identified more than 100 different types of blood cancer, while most patients may be familiar with the big three (leukaemia, lymphoma, and melanoma). However, myelodysplastic syndromes and myeloproliferative neoplasms are also prominent types of blood cancer.

Thanks to the dedicated efforts of doctors, patients, carers, and healthcare professionals, people diagnosed with blood cancer are now living longer, with a steady stream of more effective treatments entering the market each year. However, there is still much to be done to achieve a vision wherein all those diagnosed with blood cancer survive.

As we enter Blood Cancer Awareness month, a global event dedicated to spotlighting and supporting efforts to improve awareness, detection, and treatment of blood cancer, we take a look back in celebration of the achievements and breakthroughs that paved the way for todays innovations.

1832 Discovery of Hodgkins and non-Hodgkins lymphoma

Although early accounts of an illness akin to leukaemia can be traced back to Ancient Greece, the first official description of blood cancer didnt appear until 1832, when British pathologist and pioneer of preventative medicine Thomas Hodgkin used the controversial concept of micrology to identify the abnormalities in the lymphatic system.

During his time working in the pathology museum at Guys Hospital in London, Hodgkin studied several preserved specimens of human organs affected by disease. Noticing a pattern in the lymph nodes and spleen that indicated the appearance of disease, he published his findings in a paper entitled, On Some Morbid Appearances of the Absorbent Glands and Spleen.

At the time, his hypothesis appeared to fall on deaf ears, and it would take a further three decades before Hodgkins discovery was recognised.

1844 First reported case of multiple myeloma

The first well-documented case of multiple myeloma was reported in 1844 by renowned British surgeon Samuel Solly. In 39-year-old patient Sarah Newbury, Solly observed the appearance of fatigue and bone pain resulting from multiple fractures. Only four years after the patient first showed symptoms, she died, and an autopsy revealed abnormalities in the bone marrow that closely matched the autopsy findings of 45-year-old Thomas Alexander McBean.

McBeans case is perhaps the most well-known account of multiple myeloma. Similar to Newbury, McBean known to be a highly respected tradesman developed fatigue and severe pain from weak and easily broken bones. After attempts to treat McBeans symptoms through cupping, applying leeches for maintenance therapy, and therapeutic phlebotomy proved unsuccessful, his physician, Dr Thomas Watson, prescribed steel and quinine, while a sample of his urine was sent to chemical pathologist Henry Bence Jones.

Following his death in 1846, histologic examination of McBeans bone marrow revealed a red gelatiniform substance consisting of nucleated cells, some twice the size of an average blood cell.

1847 Virchow links tumours and white blood cells

By the 1840s, histology (the study of microscopic anatomy) was a recognised discipline in the scientific community. Building upon early descriptions of leukaemia by French anatomist and surgeon Alfred-Armand-Louis-Marie Velpeau, in 1847, the father of modern pathology Dr Rudolf Virchow and English physician John Hughes Bennett independently observed abnormal increases in white blood cells in patients.

Virchow was the first to argue that cancer derives from changes in normal cells. Crucially, he observed a connection between certain tumours and inflammation, noting that neoplastic tissues were often covered with leukocytes of the immune system.

As with Hodgkins discovery, Virchows theory went almost unnoticed until the 20th century.

1907 The magic bullet of immunotherapy

In the early 1900s, researchers uncovered the existence of several types of blood cancer. However, effective treatments were not available at the time. During this period, Nobel prize-winning German scientist Paul Ehrlich developed his lock-key hypothesis of molecules that specifically bind to cell receptors.

Further research led Ehrlich to develop his side-chain theory, that antibodies produced by white blood cells act as receptors on the cell membrane. For his contribution, in 1908, Ehrlich received the Nobel Prize for Medicine in the field of immunology, together with the father of innate immunity, Ilia Metschnikow, whose discovery of phagocytosis formed the foundation of cell-mediated immunity.

While they may not have known it at the time, through their work Ehrlich and Metschnikow formed the cornerstone of modern immunology, including chemoreceptor and chemotherapy concepts that revolutionised blood cancer treatment over the following century.

1942 Chemotherapy moves from trenches to treatment

In the aftermath of World War I, medical researchers noticed that the mustard gas used to make chemical weapons for the battlefield also destroyed lymphatic tissue. Early experiments showed that topically applying nitrogen mustard caused tumours to shrink in mice.

Research into the medical potential of mustard gas stagnated until 1942, when two assistant professors at Yale, Louis S Goodman and Alfred Gilman, began to study the effects of nitrogen mustard on lymphoma. Although clinical trials proved that chemicals could be used to treat cancer, the results of the study remained a closely guarded military secret until 1946.

1956 The rise of bone marrow transplants

In a milestone achievement for blood cancer research and treatment, Dr E Donnall Thomas performed the first successful bone marrow transplant in 1956. The procedure involved transplanting bone marrow between identical twins, with tissue taken from the healthy twin given to the other who had leukaemia.

In 1968, the first bone marrow transplant using a matched donor took place at the University of Minnesota. Using a blood test developed by Dr Fritz Bach, Dr Robert Good determined that the patient, a baby with a severe immune deficiency, was a human leukocyte antigen match with his nine-year-old sister.

The ground-breaking approach to donor selection paved the way for future bone marrow transplants, including the first successful bone marrow transplant with unrelated patients in 1973.

Before the birth of bone marrow transplants, patients were often treated using chemotherapy, which could be used to kill cancer cells. However, this also presented a problem: chemotherapy does not discriminate between healthy and cancer cells, meaning that if patients were given sufficient doses to kill the disease, normal cells would also be harmed. With the advent of bone marrow transplantation, these healthy cells could be replaced with donor cells, allowing for higher doses of chemotherapy in treatment.

1980s Emergence of cord blood transplants

Another source of haematological stem cells emerged in the late 80s cord blood stem cells. The remaining blood found within the umbilical cord and placenta after birth is rich in blood-producing stem cells. Cord blood collection has rarely changed since the first successful procedure occurred in 1988.

Stem cells extracted from a donated cord can be frozen for a number of years and quickly accessed when needed. Once the transplant is complete, the cells will travel into the patients bone marrow, where they will begin to grow into normal blood cells.

Recognising the need to identify and match potential donors with patients, in 1989 the Bone Marrow Donors Worldwide programme was established.

Today, the bone marrow donor registry comprises more than 39,527,166 donors and 804,246 cord blood units.

2001 FDA green lights revolutionary treatments

Innovation in blood cancer treatments ushered in a new generation of targeted and precision treatments. One such therapy was Imatinib (also known as Gleevec or Glivec), a first-generation tyrosine kinase inhibitor dubbed a magical bullet, designed to specifically target BCR-ABL tyrosine kinase.

Just over a decade after it was developed by biochemist Nicholas Lyndon, Imatinib received US Food and Drug Administration (FDA) approval in 2001. Since then, it has transformed the treatment of chronic myeloid leukaemia and non-Hodgkins lymphoma.

The following year, the regulator also approved Rituximab, a monoclonal antibody targeting CD-20 positive B-cells, as a companion treatment of chemotherapy in older diffuse large B-cell lymphoma patients.

2002Emergence of CAR-T therapy

Building on the success of cytokine-based immunotherapies, scientists continued to seek other areas where the immune system could be leveraged against tumours. Throughout the 90s, Dr James Allison spearheaded research into T-cell engineering, a revolutionary technique that formed the foundation of chimeric antigen receptor (CAR) T-cell therapy.

Dr Allisons research into the function and application of T-cells in cancer treatment greatly broadened scientific understanding of the immune system. However, the first generation of CAR T-cells proved to be clinically ineffective.

It wasnt until 2002, when Memorial Sloane Kettering Cancer Center scientists Michel Sadelain, Renier Brentjens, and Isabelle Rivire opted to push the boundaries of research, by genetically engineering T-cells with a CAR, that the technique achieved successful results.

This research paved the way for the first successful treatment of a patient with acute lymphoblastic leukaemia in 2011.

2012 The 100,000 Genomics Project begins

Unlocking the secrets of the human genome has intrigued investigators for centuries. However, the technology needed to analyse genomic and long-term clinical data is a relatively recent development. With the launch of the 100,000 Genomes Project in 2012, an international team of researchers studied the role that genes play in health and disease.

For the first time, researchers demonstrated that whole genome sequencing could be used to uncover new diagnoses across the broadest range of rare diseases. This was an entirely new approach to DNA research. Previously, DNA would be segmented into short sections, which would then be read and sequenced separately.

The 100,000 Genomes Project sparked a new wave of research exploring the clinical potential of sequencing long strands of individual DNA without cutting them into sections. With this technique, it is hoped that researchers will gain previously inaccessible insights into cancer, revealing more accurate diagnoses and treatment pathways for patients.

20162022 New treatments enter the market

Over the past few years, the number of treatments approved for blood cancer has skyrocketed. Johnson & Johnsons Darzalex (daratumumab) was a notable development for the sector. The monoclonal antibody first received FDA approval in November 2015 as a monotherapy for patients with multiple myeloma, marking it as the first CD38-directed antibody to receive regulatory approval to treat the disease. It has since gone on to receive numerous approvals for multiple myeloma designations.

As of 2022, more than 800 new cell therapies are being developed for five blood cancers, with the market for oncology cell therapies expected to exceed $37 billion in value globally by 2028.

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A history of blood cancer treatment - - pharmaphorum

Researchers discover a new class of medications that offer a safer treatment for leukemia – Interesting Engineering

Our work on an enzyme that is mutated in leukemia patients has led to the discovery of an entirely new way of regulating this enzyme, as well as new molecules that are more effective and less toxic to human cells, said Norbert Reich, a distinguished professor at the University of California, Santa Barbara, and the corresponding author of the study.

A cells epigenome is copied and maintained by an enzyme called DNMT1. For instance, this enzyme ensures that a dividing liver cell produces two liver cells rather than a brain cell.

However, some cells need to undergo differentiation to become new types of cells. For instance, bone marrow stem cells can developall the various blood cell types, which are incapable of self-replication. DNMT3A, another enzyme, manages this.

This is not a problem until a dysfunction of DNMT3A results in the production of abnormal blood cells from bone marrow. This is a prominent factor in the development of several types of leukemia as well as other cancers.

Most cancer medications are intended to attack cancer cells while only leaving healthy cells. But this is quite a challenging process; therefore, most have severe side effects.

Current leukemia medications, such as Decitabine, bind to DNMT3A in a way that disables it. So that they slow the progression of the disease by obstructing the enzyme's active site, preventing it from continuing its function.

Unfortunately, the active site of DNMT3A is virtually identical to that of DNMT1, therefore, the medication blocks epigenetic regulation in patients' 30 to 40 trillion cells. This leads to off-target toxicity- one of the drug industry's largest bottlenecks.

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Researchers discover a new class of medications that offer a safer treatment for leukemia - Interesting Engineering