Stem Cell Clinic

Exercise found to block chronic inflammation in mice – Harvard Gazette

Scientists at Harvard-affiliated Massachusetts General Hospital (MGH) have identified a previously unknown biological pathway that promotes chronic inflammation and may help explain why sedentary people have an increased risk for heart disease and strokes.

In a study to be published in the November issue ofNature Medicine, MGH scientists and colleagues at several other institutions found that regular exercise blocks this pathway. This discovery could aid the development of new therapies to prevent cardiovascular disease.

Regular exercise protects the cardiovascular system by reducing risk factors such as cholesterol and blood pressure. But we believe there are certain risk factors for cardiovascular disease that are not fully understood, said Matthias Nahrendorf of the Center for Systems Biology at MGH. In particular, Nahrendorf and his team wanted to better understand the role of chronic inflammation, which contributes to the formation of artery-clogging blockages called plaques.

Nahrendorf and colleagues examined how physical activity affects the activity of bone marrow, specifically hematopoietic stem and progenitor cells (HSPCs). HSPCs can turn into any type of blood cell, including white blood cells called leukocytes, which promote inflammation. The body needs leukocytes to defend against infection and remove foreign bodies.

When these [white blood] cells become overzealous, they start inflammation in places where they shouldnt, including the walls of arteries.

Matthias Nahrendorf

But when these cells become overzealous, they start inflammation in places where they shouldnt, including the walls of arteries, said Nahrendorf.

Nahrendorf and his colleagues studied a group of laboratory mice that were housed in cages with treadmills. Some of the mice ran as much as six miles a night on the spinning wheels. Mice in a second group were housed in cages without treadmills. After six weeks, the running mice had significantly reduced HSPC activity and lower levels of inflammatory leukocytes than the mice that simply sat around their cages all day.

Nahrendorf explains that exercising caused the mice to produce less leptin, a hormone made by fat tissue that helps control appetite, but also signaled HSPCs to become more active and increase production of leukocytes. In two large studies, the team detected high levels of leptin and leukocytes in sedentary humans who have cardiovascular disease linked to chronic inflammation.

This study identifies a new molecular connection between exercise and inflammation that takes place in the bone marrow and highlights a previously unappreciated role of leptin in exercise-mediated cardiovascular protection, said Michelle Olive, program officer at the National Heart, Lung, and Blood Institute Division of Cardiovascular Sciences. This work adds a new piece to the puzzle of how sedentary lifestyles affect cardiovascular health and underscores the importance of following physical-activity guidelines.

Reassuringly, the study found that lowering leukocyte levels by exercising didnt make the running mice vulnerable to infection. This study underscores the importance of regular physical activity, but further focus on how exercise dampens inflammation could lead to novel strategies for preventing heart attacks and strokes. We hope this research will give rise to new therapeutics that approach cardiovascular disease from a completely new angle, said Nahrendorf.

The primary authors of theNature Medicinepaper are Nahrendorf, who is also a professor of radiology at Harvard Medical School; Vanessa Frodermann, a former postdoctoral fellow at MGH who is now a senior scientist at Novo Nordisk; David Rohde, a research fellow in the Department of Radiology at MGH; and Filip K. Swirski, an investigator in the Department of Radiology at MGH.

The work was funded bygrantsHL142494 andHL139598from the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health.

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Exercise found to block chronic inflammation in mice - Harvard Gazette

Introduction to Cell Therapy – Clinical OMICs News

Sponsored content brought to you byCell Therapy Overview

CAR-T therapies have quickly shifted the direction of treatments for aggressive diseases, such as blood cancers, where previous treatments were limited. There are currently over 1000 cell and gene therapy trials and two approved cell therapies, axicabtagene ciloleucel and tisagenlecleucel, but determining cellular fitness is still a top need in moving the next generation of cell therapy treatments forward.

Both autologous and allogeneic options are among the cutting-edge therapies of today, which also comprise T cells, NK cells, and more, while using technologies like CRISPR and TALEN to address blood cancers and solid tumor. CRISPR, for example, has paved the way for new possibilities in the cell therapy space, including providing a way for researchers to develop a renewable source of NK cells to be optimized for cell therapies,1 as well as enabling more specific and targeted edits to cells in general.

Because cell therapy relies on immune cells from patients, or healthy donors in the case of allogeneic therapies, development and production is more complicated. To ensure that these cell products are potent and effective, knowing how to engineer potency and durability throughout the development and bioprocessing stages is crucial.

Knowledge of the powerful functional T cell drivers can give complex engineered immune cell therapies the edge that they need in this competitive and fast-paced environment. Legacy technologies, such as bulk ELISA or flow cytometry, can give estimates of a samples cytokine secretions, but miss the highly functional cell subsets that correlate to in vivo response. Bulk analysis is unable to analyze single cell function or identify which cells are secreting specific cytokines. Flow cytometry involves fixing and permeabilizing cells and can only provide estimates of cellular function. RNA-Seq can estimate function as well, but only shows a 0.4 correlation from RNA to protein.2 These limitations from legacy technologies remain challenges in determining function of cell products.

To address this challenge and need, IsoPlexis functional T cell biology is rooted in the ability to directly identify what each T cell secretes in a highly multiplexed manner, for the first time. High multiplexing of simultaneous true cytokines reveals most consistently intense and potent T cells. The IsoPlexis system can discover true function in single cell subsets, or highly polyfunctional cells, which correlates to response and reveals highly differentiated T cell insights.

In the initial phase of approved cell therapies, researchers published data using IsoPlexis single-cell functional cytokine detection system to demonstrate the enhanced ability to detect underlying cell therapy product heterogeneity. IsoPlexis single-cell cytokine based PCA visualizations (Figure 1) of the CAR-T product, published in JITC,3 revealed the potential to visualize donor differences.

Figure 1. Visualizing CAR-T cell functional groups and donor differences.

In an additional study, researchers used the IsoPlexis single-cell platform to correlate pre-infusion cell product data, using a metric termed Polyfunctional Strength Index (PSITM), with objective response in vivo for the first time. Importantly, existing technologies like flow cytometry and bulk ELISA did not correlate with response (Figure 2), as published in Blood.4 In contrast to flow-based systems, where cells must be fixed and permeabilized, halting biological function and trapping cytokines within the cells, IsoPlexis single-cell cytokine system measures true secretions of the full range of functional cytokines, which recruit other immune cells, destroying the tumor.

Figure 2. Polyfunctional Strength Index (PSITM) is uniquely predictive to patient response.

IsoPlexis correlative CAR-T cellular fitness metrics are defined by their ability to capture truly released cytokine function of each cell. This knowledge is being applied in advanced bioprocessing with cell product biomarkers (Figure 3) and in donor selection in allogeneic cell therapies by leaders in the cell therapy field.

Figure 3. Novel finding: CAR T cell polyfunctionality associated with outcomes.

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Approach to Personalizing Treatment of Triple-Negative Breast Cancer Shows Promise in Cell Lines – Michigan Medicine

Next, the team tested 78 approved or investigational cancer drugs against each of the cell lines, selecting the compounds based on their effectiveness in other solid-tumor cancers. After a series of initial experiments to gauge their effectiveness, 12 of the drugs were prioritized for deeper analysis.

Among these, the research group found six drugs that showed promising results against tumors with particular molecular features suggesting the approach is a solid first step toward developing robust biomarkers of drug response in triple-negative breast cancer.

Many other breast cancer subtypes are defined by the pathways that you would use to target them for example, youd treat HER2-positive breast cancer with a HER-2 inhibitor, says senior study author Sofia Merajver, M.D., Ph.D., a professor of internal medicine and epidemiology at the U-M. Triple-negative breast cancer is defined by its lack of hormone receptors and HER2 expression, which makes it much more difficult to target. We needed to do better.

Since cancer often quickly develops resistances against individual drugs, the researchers also wanted to use their multi-omic approach to look for ideal combinations of drugs.

The idea is that if we find a marker that is particularly high in drug-resistant cells, we might be able to make the cells more responsive to treatment by adding a drug that also targets that marker, says senior study author Matthew Soellner, Ph.D., an assistant professor of internal medicine and chemistry at U-M, and an affiliate faculty member of the U-M Life Sciences Institute. Ultimately, we found we could make most of the cell lines more sensitive to our target drug it worked better than we had hoped for.

The research was supported by the National Institutes of Health (1R21CA218498), the Breast Cancer Research Foundation, Tempting Tables, The Rose Run, and the Kathy Bruk Pearce Research Fund of the U-M Rogel Cancer Center.

Additional authors include Eric J. Lachacz, Nathalie M. Vandecan, Peter J. Ulintz, Liwei Bao, John P. Lloyd, Joel A. Yates and Aki Morikawa, all of U-M.

Paper cited: Molecular determinants of drug response in TNBC cell lines, Breast Cancer Research and Treatment. DOI: 10.1007/s10549-019-05473-9

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miR-1305 Inhibits The Progression Of Non-Small Cell Lung Cancer By Reg | CMAR – Dove Medical Press

Yuxing Cai,1 Yi Hao,2 HaiFeng Ren,3 ZhiGuo Dang,3 Hui Xu,1 Xiangfei Xue,1 Yan Gao3

1Department of Respiratory Medicine, Baoji Central Hospital, Baoji, 721008, Peoples Republic of China; 2Department of Pediatric Surgery, Baoji Maternal and Child Health Hospital, Baoji, 721008, Peoples Republic of China; 3Department of Respiratory Medicine, People Hospital BaoJi City, Baoji, 721001, Peoples Republic of China

Correspondence: Yan GaoDepartment of Respiratory Medicine, People Hospital BaoJi City, No. 24 Xinhua Street, Weibin District, Baoji City, Shanxi Province 721001, Peoples Republic of ChinaEmail zhungao703730393@126.com

Background: Increasing evidence has suggested the critical implication of microRNAs (miRNAs) in the initiation and progression of non-small cell lung cancer (NSCLC). Previous studies have shown the tumor-suppressive function of miR-1305 in cancer; however, the role of miR-1305 in NSCLC has not been fully understood.Methods: The expression of miR-1305 in NSCLC was detected by RT-qPCR. The influence of miR-1305 on the growth of NSCLC cells was determined via Cell Counting Kit 8 (CCK-8), colony formation and FACS analysis. The targets of miR-1305 were predicted with the miRDB database. Luciferase reporter assay was performed to investigate the binding between miR-1305 and 3-UTR of MDM2. Western blot was applied to check the expression of MDM2 with miR-1305.Results: Here, we found that miR-1305 was down-regulated in NSCLC tissues and cell lines. Decreased miR-1305 was significantly correlated with the metastasis and poor prognostics of NSCLC patients. Overexpression of miR-1305 inhibited the proliferation and migration and promoted the apoptosis of NSCLC cells. Bioinformatics and luciferase assay uncovered that the mouse/murine double minute 2 (MDM2) was a target of miR-1305. miR-1305 bound the 3-untranslated region (UTR) of MDM2 and decreased the expression of MDM2 in NSCLC cells. As MDM2 was a negative regulator of p53, decreased MDM2 by miR-1305 up-regulated the abundance of p53 in NSCLC cells. Restoration of MDM2 markedly attenuated the suppressive role of miR-1305 in the proliferation and migration of NSCLC cells.Conclusion: The findings provided novel mechanism of miR-1305/MDM2 signaling in regulating the progression of NSCLC, suggesting miR-1305 as a promising target for the treatment of NSCLC.

Keywords: NSCLC, miR-1305, MDM2, p53

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Genentech’s Gazyva (obinutuzumab), in Combination With Standard of Care, More Than Doubles the Percentage of Lupus Nephritis Patients Achieving…

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced data from the Phase II NOBILITY study, investigating the safety and efficacy of Gazyva (obinutuzumab) for adults with proliferative lupus nephritis. The study met the primary endpoint with Gazyva, in combination with standard of care (mycophenolate mofetil or mycophenolic acid and corticosteroids), demonstrating superiority compared to placebo plus standard of care. Patients treated with Gazyva showed increasing rates of complete renal response (CRR) from week 52 to week 76, with 40% of patients in the Gazyva group achieving CRR, compared to 18% of patients in the placebo group at week 76 (p=0.007). Gazyva additionally met key secondary efficacy endpoints showing improved overall renal response (complete or partial renal responses) and serologic markers of disease activity as compared to placebo. No new safety signals were observed with Gazyva in the study at the time of this analysis. Through week 76, serious adverse events (24% vs. 29% in placebo group) and serious infections (6% vs.18% in placebo group) were not increased with Gazyva. These data will be presented at the 2019 American College of Rheumatology (ACR) Annual Meeting in Atlanta, Georgia, on November 10, 2019 (Abstract 939).

We are very encouraged by the positive results from the NOBILITY study, which suggest that Gazyva may provide a clinically meaningful benefit for adults with proliferative lupus nephritis; a condition for which there is a strong need for more effective and targeted treatment options, said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. These results support the continued development of Gazyva for people with lupus nephritis and underscore our longstanding commitment to pursue new treatment options that may benefit the lupus community.

Lupus nephritis is a severe and potentially life-threatening manifestation of systemic lupus erythematosus resulting from inflammation of the kidneys, with proliferative lupus nephritis being the most severe form and associated with high-risk of end-stage renal disease and death. In September 2019, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to Gazyva for adults with lupus nephritis based on the Phase II NOBILITY study data. Genentech will initiate a Phase III study for Gazyva in lupus nephritis in 2020.

Phase II data from the NOBILITY study was also presented as a late-breaking oral presentation at the American Society of Nephrologys (ASN) Kidney Week 2019 in Washington, DC, on November 8, 2019 (Abstract FR-OR136).

An audio webcast for analysts and investors on the Phase II NOBILITY study data will be held on Tuesday, November 12, 2019 from 4:30-5:30 p.m. CET / 10:30-11:30 a.m. ET. Further details are available here.

Lupus nephritis overwhelmingly impacts women, particularly young women of color. About 90% of those diagnosed with lupus are women, and African American, Hispanic, Native American and Asian American women are two to three times more likely than Caucasian women to get lupus. Genentech is committed to addressing barriers to clinical trial participation and advancing inclusive research to create new standards for clinical studies. Genentech is taking action to recruit a broader, more diverse population of participants into clinical trials, including diseases such as lupus nephritis, to ensure clinical trial participants more closely reflect those impacted by the disease for which a medicine is being studied. To learn more about Genentechs efforts in this area, please visit https://www.gene.com/inclusiveresearch.

About the NOBILITY Study

The Phase II, randomized, double-blind, placebo-controlled, multi-center study, NOBILITY (NCT02550652), compared the safety and efficacy of Gazyva, combined with mycophenolate mofetil (MMF) or mycophenolic acid (MPA) and corticosteroids, to placebo, combined with MMF or MPA and corticosteroids, in adult patients with ISN/RPS 2003 class III or IV proliferative lupus nephritis. The study enrolled 125 people who were randomized to receive Gazyva or placebo infusions on days 1, 15, 168, and 182. The primary endpoint was the proportion of participants who achieved a protocol-defined complete renal response (CRR) at 52 weeks. Key secondary endpoints included overall renal responses (complete or partial renal response) and serologic markers of disease activity, as compared to placebo. Patients were followed in a blinded fashion through week 104, and patients with persistent B-cell depletion are being followed for safety and continued B-cell measurements.

About Lupus Nephritis

Lupus nephritis is a severe and potentially life-threatening disorder of the kidneys. Lupus nephritis is one of the most severe manifestations of systemic lupus erythematosus (SLE), an autoimmune disease where a person's own immune system attacks healthy cells and organs, including, in the case of lupus nephritis, the kidneys. This causes kidney inflammation and may lead to blood and/or protein in the urine, high blood pressure, poor kidney function, or kidney failure. An estimated 1.5 million Americans are affected by lupus, with approximately 70% of cases representing SLE. Up to 60% of people with SLE will develop lupus nephritis, and up to 25% of people with the condition develop end-stage renal disease. Lupus overwhelmingly impacts women, particularly young women of color. About 90% of those diagnosed with lupus are women, and African American, Hispanic, Native American and Asian American women are two to three times more likely than Caucasian women to get lupus. Currently, there is no cure for lupus or lupus nephritis.

About Gazyva

Gazyva is an engineered monoclonal antibody designed to attach to CD20, a protein found only on certain types of B-cells. It is thought to work by attacking targeted cells both directly and together with the body's immune system. Gazyva is part of a collaboration between Genentech and Biogen. Combination studies investigating Gazyva with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are underway across a range of blood cancers.

Gazyva Indications

Gazyva (obinutuzumab) is a prescription medicine used:

Important Safety Information

The most important safety information patients should know about Gazyva

Patients must tell their doctor right away about any side effect they experience. Gazyva can cause side effects that can become serious or life-threatening, including:

Who should not receive Gazyva:

Patients should NOT receive Gazyva if they have had an allergic reaction (e.g., anaphylaxis or serum sickness) to Gazyva. Patients must tell their healthcare provider if they have had an allergic reaction to obinutuzumab or any other ingredients in Gazyva in the past.

Additional possible serious side effects of Gazyva:

Patients must tell their doctor right away about any side effect they experience. Gazyva can cause side effects that may become severe or life threatening, including:

The most common side effects of Gazyva in CLL were infusion reactions, low white blood cell counts, low platelet counts, low red blood cell counts, fever, cough, nausea, and diarrhea.

The safety of Gazyva was evaluated based on 392 patients with relapsed or refractory NHL, including FL (81%), small lymphocytic lymphoma (SLL) and marginal zone lymphoma (MZL) (a disease for which Gazyva is not indicated), who did not respond to or progressed within six months of treatment with rituximab product or a rituximab product-containing regimen. In patients with follicular lymphoma, the profile of side effects that were seen were consistent with the overall population who had NHL. The most common side effects of Gazyva were infusion reactions, low white blood cell counts, nausea, fatigue, cough, diarrhea, constipation, fever, low platelet counts, vomiting, upper respiratory tract infection, decreased appetite, joint or muscle pain, sinusitis, low red blood cell counts, general weakness and urinary tract infection.

A randomized, open-label multicenter trial (GALLIUM) evaluated the safety of Gazyva as compared to rituximab product in 1,385 patients with previously untreated follicular lymphoma (86%) or marginal zone lymphoma (14%). The most common side effects of Gazyva were infusion reactions, low white blood cell count, upper respiratory tract infection, cough, constipation and diarrhea.

Before receiving Gazyva, patients should talk to their doctor about:

Patients should tell their doctor about any side effects.

These are not all of the possible side effects of Gazyva. For more information, patients should ask their doctor or pharmacist.

Gazyva is available by prescription only.

Report side effects to the FDA at (800) FDA-1088, or http://www.fda.gov/medwatch. Report side effects to Genentech at (888) 835-2555.

Please visit http://www.Gazyva.com for the Gazyva full Prescribing Information, including BOXED WARNINGS, for additional Important Safety Information.

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

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Genentech's Gazyva (obinutuzumab), in Combination With Standard of Care, More Than Doubles the Percentage of Lupus Nephritis Patients Achieving...

New Data Uncover Deeper Insight into Tebentafusp (IMCgp100) Clinical Activity in Patients with Advanced Melanoma, Including Uveal – Business Wire

OXFORDSHIRE, England & CONSHOHOCKEN, Pa. & ROCKVILLE, Md.--(BUSINESS WIRE)--Immunocore Limited, a leading T cell receptor (TCR) biotechnology company, presented new findings from its Phase 1/2 tebentafusp (IMCgp100) clinical trial programme demonstrating a correlation between treatment-induced immune response and improvement in overall survival and tumour shrinkage, in patients with advanced uveal and cutaneous melanoma. The new analyses from two clinical trials (IMCgp100-101, IMCgp100-102) were presented at the Society for Immunotherapy of Cancer (SITC) Annual Meeting in National Harbor, Maryland.

We are gaining valuable insights from our clinical data to further our understanding of the mechanism of action of our bispecific, soluble TCR, said Bahija Jallal, Chief Executive Officer of Immunocore. Advancing the science underlying TCR recognition of antigens supports our efforts to further develop our platform and maximize its value on behalf of patients.

Tebentafusp is an investigational novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. It is engineered to specifically target gp100, a lineage antigen expressed in melanocytes and melanoma, and is the first molecule developed using Immunocores ImmTAC technology platform designed to redirect and activate T cells to recognise and kill tumour cells. Pivotal tebentafusp clinical trials are currently underway in metastatic uveal melanoma (UM), a rare form of eye cancer.

When using a therapy designed to induce an immune response, its not unexpected to see inflammatory events like rash or cytokine response syndrome, said Alexander N. Shoushtari, M.D., study investigator and medical oncologist at Memorial Sloan Kettering Cancer Center in New York. While these were general low-grade events that resolved with treatment and time, it was interesting to see their potential connection to overall survival and other clinical outcomes. These findings are encouraging and will help to inform future research and treatment protocols.

SITC Presentation Highlights:

Induction of serum CXCL10 by tebentafusp, a gp100-CD3 bispecific fusion protein, was associated with survival in uveal melanoma in a Phase 1/2 study

The goal of this analysis was to increase understanding of the biological effects of tebentafusp and association between rash seen with treatment, CXCL10 and clinical outcomes in UM. Researchers focused on the initial 42 patient cohort enrolled in IMCgp100-102, a Phase 1/2 study in patients with HLA-A2+ positive advanced UM. Patients were treated using a weekly intra-patient dose-escalation regimen and the occurrence of rash within 21 days following treatment initiation was evaluated as a predictor of overall survival.

The findings showed a transient increase in peripheral cytokines after treatment with tebentafusp, reaching maximal changes at 8-24 hours post treatment, with CXCL10 having the greatest increment between 12-24 hours. Patients treated with tebentafusp experienced induced type 1/2 IFN pathways and neutrophil, eosinophil signatures and reduced CD4, CD8 and NK cell signatures in the blood. Tebentafusp-treated patients with rash and those with a greater increase in serum CXCL10 following the first treatment dose appeared to be associated with improved overall survival. In a multivariate Cox proportional hazards model, both rash (p<0.001) and CXCL10 induction (p=0.01) were independent predictors of survival.

Cytokine release syndrome following treatment with tebentafusp, a novel bispecific TCR-anti-CD3 directed against gp100, in patients with advanced melanoma

The goal of this analysis was to better understand the incidence, severity and resolution of cytokine release syndrome (CRS) following tebentafusp treatment, an adverse event commonly associated with CD3-bispecifics, and its association with clinical outcomes in advanced melanoma. Researchers analysed data from IMCgp100-101, a Phase 1 first-in-human clinical trial assessing the safety and tolerability of tebentafusp in 84 HLA-A2+ patients with metastatic melanoma (n=61 cutaneous, n=19 uveal, n=4 other) resistant to standard treatment regimens or for which no standard treatments exist. This post-hoc analysis evaluated adverse events, serious adverse events, vital signs, and concomitant medications reported by investigators to identify episodes of CRS.

The findings show that patients treated with tebentafusp experienced a low incidence of severe CRS. Despite no corticosteroid pre-treatment, CRS occurrence was generally low grade, reversible with standard management (i.e., IVF and short course corticosteroids), decreased in frequency and severity after the initial doses, and infrequently led to the discontinuation of treatment. The most frequent CRS adverse events were mild-to-moderate fever, fatigue, nausea, hypotension and headache. Patients with a < 1C increase in body temperature eight hours following treatment were less likely to develop subsequent moderate or higher-grade CRS. Consistent with tebentafusps hypothesized mode of action, transient increases in peripheral cytokines occurred within hours of treatment administration, and tended to be greater in patients with higher grade CRS. The incidence of CRS following the first dose of tebentafusp appeared to be associated with the greatest reductions in tumour size.

- Ends -

About ImmTAC MoleculesImmunocores proprietary T cell receptor (TCR) technology generates a novel class of bispecific biologics called ImmTAC (Immune mobilising monoclonal TCRs Against Cancer) molecules that are designed to redirect the immune system to recognise and kill cancerous cells. ImmTAC molecules are soluble TCRs engineered to recognise intracellular cancer antigens with ultra-high affinity and selectively kill these cancer cells via an anti-CD3 immune-activating effector function. Based on the demonstrated mechanism of T cell infiltration into human tumours, the ImmTAC mechanism of action holds the potential to treat hematologic and solid tumours, regardless of mutational burden or immune infiltration, including immune cold low mutation rate tumours.

About TebentafuspTebentafusp is a novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. Tebentafusp specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma, and is the first molecule developed using Immunocores ImmTAC technology platform designed to redirect and activate T cells to recognise and kill tumour cells. Tebentafusp has Fast Track Designation and Orphan Drug Designation in the US and Promising Innovative Medicine designation under the UK Early Access to Medicines Scheme for metastatic uveal melanoma. For more information about enrolling tebentafusp clinical trials for metastatic uveal melanoma, please visit ClinicalTrials.gov (NCT03070392).

About Uveal MelanomaUveal melanoma is a rare and aggressive form of melanoma, which affects the eye. Metastatic uveal melanoma typically has a poor prognosis and has no currently accepted optimal management or treatment.1,2 Although it is the most common primary intraocular malignancy in adults, the diagnosis is rare, with approximately 8,000 new patients diagnosed globally each year (1,600-2,000 cases/year in the US).3,4,5 Up to 50% of people with uveal melanoma will eventually develop metastatic disease.1,2 When the cancer spreads beyond the eye, only approximately half of patients will survive for one year.6

About Immunocore

Immunocore is a leading T cell receptor (TCR) biotechnology company working to create first-in-class biological therapies to address unmet patient needs in oncology as well as infectious and autoimmune diseases. Immunocore has a pipeline of proprietary and partnered programmes in development. Collaboration partners include Genentech, GlaxoSmithKline, AstraZeneca, Lilly, and the Bill and Melinda Gates Foundation. Immunocore is headquartered in Oxfordshire, UK, with offices in Conshohocken, PA and Rockville, MD, US. The Company is privately held by a broad international investor base. For more information, please visit http://www.immunocore.com.

Dr. Shoushtari serves on Immunocores scientific advisory board.

1 Damato BE, Dukes J, Goodall H, Carvajal RD. Tebentafusp: T cell redirection for the treatment of metastatic uveal melanoma. Cancers. 2019;11(7):971.

2 Carvajal, RD, Schwartz, GK, Tezel, T, et al., 2017. Metastatic disease from uveal melanoma: treatment options and future prospects. British Journal of Ophthalmology, 101(1), 38-44.

3 Pandiani C, Branger GE, Leclerc J, Ballotti R, Bertolotto C. Focus on cutaneous and uveal melanoma specificities. Genes Dev. 2017;31(8):724-743.

4 Jovanovic P, Mihajlovic M, Djordjevic-Jocic J, Vlajkovic S, Cekic S, Stefanovic V. Ocular melanoma: an overview of the current status. Int J Clin Exp Pathol. 2013;6(7):1230-1244.

5 About ocular melanoma. Ocular Melanoma Foundation website. http://www.ocularmelanoma.org/about-om.htm. Accessed September 2019.

6 Rantala ES, Hernberg M, Kivel TT. Overall survival after treatment for metastatic uveal melanoma: a systematic review and meta-analysis. Melanoma Res 2019

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New Data Uncover Deeper Insight into Tebentafusp (IMCgp100) Clinical Activity in Patients with Advanced Melanoma, Including Uveal - Business Wire