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Adaptimmune Announces Initiation of Study to Evaluate SPEAR T-Cell Therapy Targeting AFP in Liver Cancer – GlobeNewswire (press release)

May 10, 2017 07:30 ET | Source: Adaptimmune Therapeutics plc

PHILADELPHIA and OXFORD, U.K., May 10, 2017 (GLOBE NEWSWIRE) -- Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, today announced that it has initiated the first site for its AFP SPEAR T-cell study in patients with locally advanced or metastatic hepatocellular carcinoma, the sixth most common cancer worldwide. This study is now open for enrollment.

This is Adaptimmunes second wholly-owned therapeutic candidate to enter clinical trials. The Company already has ongoing studies to evaluate its T-cell therapy targeting the MAGE-A10 cancer antigen in patients with non-small cell lung cancer, urothelial cancer, melanoma, or head and neck cancers.

We are excited to initiate this study to evaluate our AFP T-cell therapeutic candidate in patients with hepatocellular carcinoma, said Rafael Amado, Adaptimmunes Chief Medical Officer. HCC is one of the more common and deadly types of cancer worldwide and there is an urgent need for effective therapies for advanced disease.

This is a Phase I, open label, dose escalation study designed to evaluate the safety and anti-tumor activity of Adaptimmunes alpha fetoprotein (AFP) therapeutic candidate in hepatocellular carcinoma (HCC). The study will enroll up to 30 patients with measurable, histologically confirmed HCC, not amenable to resection or loco-regional therapy, and with progressive disease. The primary objective of the study is to evaluate the safety and tolerability of this second-line therapy (post-sorafenib) in patients with AFP-positive HCC. Additional objectives include anti-tumor activity, persistence of genetically modified cells in the body, and evaluation of the phenotype and functionality of genetically modified cells isolated from peripheral blood or tumor post infusion.

Additional information about this study is available at http://www.clinicaltrials.gov by searching on NCT03132792.

About Hepatocellular (Liver) Cancer A cancer that starts in the liver is called primary liver cancer. Hepatocellular carcinoma is the most common type of liver cancer in adults. Many patients who develop liver cancer have long-standing cirrhosis (scar tissue formation from liver cell damage), and early detection can be difficult because signs and symptoms often do not appear until later stages. It is estimated that approximately 40,710 new cases of primary liver cancer and intrahepatic bile duct cancer will be diagnosed (about 29,200 in men and 11,510 in women, and about 28,920 people will die from these cancers (about 19,610 men and 9,310 women) in the United States in 2017.

About Adaptimmune Adaptimmune is a clinical-stage biopharmaceutical company focused on the development of novel cancer immunotherapy products. The Companys unique SPEAR (Specific Peptide Enhanced Affinity Receptor) Tcell platform enables the engineering of T-cells to target and destroy cancer, including solid tumors. Adaptimmune has a number of proprietary clinical programs, and is also developing its NY-ESO SPEAR T-cell program under a strategic collaboration and licensing agreement with GlaxoSmithKline. The Company is located in Philadelphia, USA and Oxfordshire, U.K. For more information, please visit http://www.adaptimmune.com

Forward-Looking Statements This release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 (PSLRA). These forward-looking statements involve certain risks and uncertainties. Such risks and uncertainties could cause our actual results to differ materially from those indicated by such forward-looking statements, and include, without limitation: the success, cost and timing of our product development activities and clinical trials and our ability to successfully advance our TCR therapeutic candidates through the regulatory and commercialization processes. For a further description of the risks and uncertainties that could cause our actual results to differ materially from those expressed in these forward-looking statements, as well as risks relating to our business in general, we refer you to our Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on March 13, 2017, and our other SEC filings. The forward-looking statements contained in this press release speak only as of the date the statements were made and we do not undertake any obligation to update such forward-looking statements to reflect subsequent events or circumstances.

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Adaptimmune Announces Initiation of Study to Evaluate SPEAR T-Cell Therapy Targeting AFP in Liver Cancer - GlobeNewswire (press release)

Phase 1 Trial of CAR-T Cell Therapy for Head and Neck Cancer – Cancer Therapy Advisor

Cancer Therapy Advisor

Phase 1 Trial of CAR-T Cell Therapy for Head and Neck Cancer Cancer Therapy Advisor Description: For this single-arm, phase 1 study (ClinicalTrials.gov Identifier: NCT01818323), researchers are evaluating whether patients with squamous cell cancer of the head and neck will respond to autologous T4+ positive T cells administered ...

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Phase 1 Trial of CAR-T Cell Therapy for Head and Neck Cancer - Cancer Therapy Advisor

Antiplatelet Drugs Could Boost Effectiveness of Adoptive T Cell Therapy – Bioscience Technology

Platelets, small fragments of large cells that are a very abundant component of blood, and best known for their role in blood-clotting, help hide cancer from the immune system by suppressing T cells, according to a new study.

Now, in preclinical studies, researchers led by Zihai Li, M.D. Ph.D., chair of the Medical University of South Carolinas Department of Microbiology and Immunology found adoptive T cell therapy was more effective against melanoma when combined with common platelet-inhibitors, such as aspirin.

A disorder known as thrombocytosis, where a patient has excess platelet product, has been associated with the progression of multiple cancer types. However, how platelets change T cell immunity to encourage tumor growth was not well understood and this study sought to investigate the role more closely.

A molecule called TGF-beta is linked to suppression of the cancer-fighting activity of T cells, the study found. Immunologists have been studying TGF-beta for more than 30 years as it regulates many aspects of the immune system.

More importantly, Lis team found a protein called GARP, on the surface of the platelets, acts like a molecular hook that binds to and activates TGF-beta.

We found for the first time that the GARP, TGF-beta complex is a key mechanism utilized by platelets to subvert T cell immunity, Li said.

The first indication that the bodys clotting system might play a role in suppressing cancer-fighting T cells, was when scientists observed melanoma mouse models with genetically defective platelets.

In the mice with genetically defective platelets, T cells that were isolated and then primed to recognize tumor cells were much more active when reinjected into the mice, and tumors grew significantly more slowly than in animals with normal platelets.

Platelets and T cells isolated from mouse and human blood were observed, and both showed the T cell response was suppressed by platelets with activated clotting activity. Using mass spectrometry, the team identified the molecule with the most T cell suppression was TGF-beta.

Next, Li investigated what would happen if the platelets couldnt activate TGF-beta. They genetically modified mice without the molecular hook GARP, and found that once the platelets didnt have the ability to grab and activate TGF-beta, they could not suppress the cancer-fighting T cells. The T cell immunotherapy was more effective at controlling melanoma.

In a final experiment, the team tested melanoma models of mice with normal platelets who received adoptive T cell therapy, in combination with two antiplatelet drugs, aspirin and clopidogrel. They found that animals who received the antiplatelet drugs survived longer and relapsed less.

One popular form of current immunotherapy is so-called checkpoint inhibitors. Li and his team are about to launch a clinical trial to test the combination of checkpoint inhibitors and aspirin and clopidogrel for advanced cancers.

Im very excited about this, Li said. We can test simple, over-the-counter antiplatelet agents to really improve immunity and make a difference in how to treat people with cancer.

The findings were published May 5 in Science Immunology.

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Antiplatelet Drugs Could Boost Effectiveness of Adoptive T Cell Therapy - Bioscience Technology

First public sector stem cell bank to come up at KGMU – Times of India

LUCKNOW: In what may come as a relief to over 1 lakh patients of thalassemia in India, a public sector stem cell bank is set to come up at UP's King George's Medical University here. A project of the university's transfusion medicine department, the stem cell bank would roll out stem cell therapy to patients of thalassemia and sickle cell anaemia. The proposal is awaiting clearance from state department of medical education.

Stem cells are omnipotent and can take shape of any cell inside the body. If infused in the pancreas, stem cells will become pancreatic while in the liver, they will become liver cells.

These are found in human bone marrow and can be derived from the umbilical cord which contains blood vessels that connect baby in the womb to the mother to ingest nutrition required for development.

Research on the therapeutic use of stem cells is underway in US, Europe, China, South East Asia besides India. In UP, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS) and KGMU are both trying to explore the potential of stem cells to treat various health problems. SGPGI has, so far, restricted itself to use of allogenic (stem cells derived from bone marrow of a person), while KGMU has used stem cells derived from the umbilical cord.

Head of transfusion medicine department of KGMU, Prof Tulika Chandra said, "Several private sector stem cell banks like Life Cell and Cord Life India are operating in India but they serve only those who have deposited the baby's cord, while our bank will help everyone."

KGMU has sustained access to umbilical cord because of a very developed obstetrics and gynaecology department. The cord is gathered from the placenta in the uterus of pregnant women which nourishes and maintains the baby through the umbilical cord.

Sources in medical education department said the proposal is worth Rs 9 crore including infrastructure cost. "Stem cell bank promises to become financially self-sustaining within 2-3 years of inception," said a directorate officer.

Talking about why children with thalassemia and sickle cell anaemia were chosen, Chandra said, "Global literature shows umbilical cord stem cells can induce extraordinary results on such children. In fact, success rate is around 70-75% and higher score can be achieved if therapy is provided at an earlier age."

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First public sector stem cell bank to come up at KGMU - Times of India

Oncology Nurses Must Watch for CAR T-Cell Therapy Side Effects – Cancer Network

It is increasingly important that oncology nurses and other healthcare providers recognize cytokine release syndrome (CRS) and other side effects that can be triggered by anticancer treatment with engineered chimeric antigen receptor (CAR) T-cell therapies, and that they understand the importance of early detection, a speaker emphasized at the Oncology Nursing Society (ONS) 42nd Annual Congress, held May 47 in Denver.

Careful monitoring is essential for early detection of CAR T-cell side effects, said study coauthor Brenna Hansen, BSN, RN, OCN, a research nurse specialist at the Center for Cancer Research, National Cancer Institute, Bethesda, Maryland. Early recognition of symptoms results in early intervention and safe management of the patient by the multidisciplinary team.

CAR T-cell therapy involves equipping immune T cells with engineered receptors to facilitate immune attack on tumor cells expressing specific surface proteins. Patient T cells are collected and modified in a lab to express cancer-specific receptors. These are then infused back into the patient.

CAR T-cell therapies show promise against hematologic malignancies and other cancers but can trigger a range of initially subtle but potentially life-threatening side effects. Perhaps chief among these adverse reactions is CRS and neurologic side effects that might or might not occur with CRS. Most of these are reversible with corticosteroids or other treatment.

CRS symptoms include fever, tachycardia, and hypotension occurring within a week (typically 47 days) after CAR T-cell infusion, though CRS can occur more quickly. Ive seen CRS as soon as a day after infusion, Hansen cautioned.

Heart arrhythmias, fatigue, hypoxia, pulmonary edema, pneumonitis, electrolyte imbalances, nausea, vomiting, diarrhea, cytopenias, infections, elevated creatinine kinase, myalgia, and muscle weakness can all be signs of CRS.

Neurologic side effects can include tremors, headaches, confusion, loss of balance, trouble speaking, encephalopathy, seizures, long periods of somnolence, and sometimes, hallucinations, Hansen noted.

These symptoms can be subtle initially. Hansen described a CAR T-cell therapy patients transportation by ambulance to the hospital after detection of a subtle hand tremor because clinicians were concerned it could quickly worsen.

CAR T-cell therapies can also trigger receptor/cell-type specific side effects such as CAR19-associated B-cell aplasia and graft-vs-host disease. New side effects will likely emerge as new targets are found and CAR T-cell therapies become more commonly administered, she predicted.

Nurses play key roles in every stage of CAR T-cell toxicity monitoring and management, from inpatient monitoring at the bedside, including frequent assessments and checks of vital signs during high-risk periods, to outpatient and long-term monitoring, Hansen said.

Outpatient monitoring for patients who are infused as outpatients, or post-discharge, is key to spotting delayed toxicities, she emphasized. Clinic and triage nurses play key roles in the timely recognition of late CAR T-cell side effects.

Long-term monitoring is important, as well. Home oncology clinic nurses should monitor serum IgG (IVIG) and blood cell counts with differential.

If symptoms become severe, cells may be tempered with tocilizumab or corticosteroids, she said. However, this is avoided if possible to prevent damaging the anti-malignancy effects of the CAR T cells.

It is crucial that nursing staff be educated on side effects unique to CAR T-cell treatments, and that nursing guidance be provided specifying the signs and symptoms that should be communicated to patients other healthcare providersand patients themselvesto allow early detection and intervention. Having a written plan can help prevent confusion and provide clear guidelines for the patients care, she noted.

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Oncology Nurses Must Watch for CAR T-Cell Therapy Side Effects - Cancer Network

Aspirin, other antiplatelet drugs boost T-cell therapy in mice with … – FierceBiotech

Engineered T-cell therapies, a promising way to prime a patients immune system against cancer, dont work for everyone. Scientists from the Medical University of South Carolina (MUSC)found one possible explanation that can be targeted: blood platelets.

The immune system sees tumors, or uncontrolled cell growth, as part of the self, which allows cancer to evade immune attack. In adoptive T-cell therapy, a patients own T cells are isolated from his or her blood, and then primed to recognize tumor cells.

Previous research has shown that some cancers curb T-cell activity and that platelets, a component of blood responsible for clotting, might make cancer worse. The MUSC team, led by senior author Zihai Li, M.D., Ph.D.,found that platelets help cancer to hide by secreting a molecule, TGF-beta, that suppresses T cells.

RELATED: New culture method boosts T cells' ability to recognize multiple cancers

While most TGF-beta is inactive, the researchers found that GARP, a molecular hook on the surface of platelets, traps and activates TGF-beta. As a result, platelets become the main source of TGF-beta used by tumor cells to tamp down on T-cell function, according to a statement.

The team ran a battery of preclinical trials, finding that a T-cell therapy more effectively awoke the immune system when given alongside common antiplatelet drugs, such as aspirin.

First, they noticed that melanoma tumors grew more slowly in mice with defective platelets than in mice with normal platelets. Adoptive T-cell therapy was more effective in genetically modified mice without GARP. And mice with normal platelets and melanoma that were given T-cell therapy along with aspirin and clopidogrelsurvived longer and relapsed less, according to the statement. But antiplatelet drugs alone did not fight the cancer.

"We can test simple, over-the-counter antiplatelet agents to really improve immunity and make a difference in how to treat people with cancer, Li said. The study was published in Nature Immunology.

This study could lay the foundation for further work testing antiplatelet approaches in melanoma and other cancers. Melanoma is not currently treated with adoptive T-cell therapy, but with checkpoint inhibitors, such as Bristol-Myers Opdivo and Yervoy.

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Aspirin, other antiplatelet drugs boost T-cell therapy in mice with ... - FierceBiotech

Stem cells therapy for naturally occurring intervertebral disc disease – Medical Xpress

May 9, 2017 Credit: Vetsuisse Faculty, UZH

The intervertebral disc is the "shock absorber" between the vertebrae of the spine, cushioning every step, bend and jump. If the fibrocartilage tissue in the spine degenerates over time, an intervertebral disc can "slip" pinching the medulla or nerves. The consequences include intense pain or even paralysis. Dogs and people are often susceptible to this disease. Since intervertebral discs themselves cannot regenerate, the affected disc material is removed in an operation that can be performed on both people and animals. The pressure on the nerves and medulla disappears, but the degeneration of the disc remains.

Frank Steffen, neurologist at the Clinic for Small Animal Surgery at the Vetsuisse Faculty of the University of Zurich, has developed a stem cell therapy for the condition. Stem cells are multipotent cells that can be differentiated into various cell types. Steffen hopes that the stem cells will possibly form new disc cartilage once injected into a damaged disc. His study on three sick German shepherds demonstrate that treatment with the body's own stem cells is well tolerated an important first step.

Gaining knowledge directly from the afflicted animal

Research on intervertebral disc regeneration is frequently performed using animal testing. At the Clinic for Small Animal Surgery in Zurich, researchers have taken another path: "Since we treat numerous dogs who spontaneously sustain a slipped disc every year, we have been able to gain important knowledge directly from animals that are actually afflicted with this disease," Steffen explains. "Due to the similarity in pathology and the course of the illness, conclusions can presumably be drawn for the treatment of affected persons as well." The project for the development of stem cell therapy in dogs is being conducted in cooperation with Swiss Paraplegic Research (SPR) in Nottwil, Switzerland.

With the permission of the dog owners, Steffen and his team removed stem cells from the marrow of the pelvic bone of the affected animals. After the cleaning and preparation of the cell material in the laboratory, the stem cells were injected into the degenerated intervertebral disc during an operation. "Our objective is for the stem cells to trigger cellular and molecular repair processes and, ideally, to form new intervertebral disc cells in order to contribute to the regeneration of the tissue," Steffen says.

After tolerability, check effectiveness

The results are promising: The three dogs tolerated the injections of their own stem cells and the researchers have determined no negative effects. However, later X-rays and magnetic resonance tomographies did not show clear indications that the damaged discs have regenerated in comparison with the control group.

Steffen says, "Proving the tolerability of the therapy was our first important step." Now, he is working on the effectiveness of the stem cell injections with the targeted addition of growth factors. "If our method proves successful one day, it would be a pioneering step for human medicine as well," the neurologist says.

Explore further: MRI can visualize effects of traction on herniated discs

More information: Frank Steffen et al. Bone Marrow-Derived Mesenchymal Stem Cells as Autologous Therapy in Dogs with Naturally Occurring Intervertebral Disc Disease: Feasibility, Safety and Preliminary Results, Tissue Engineering Part C: Methods (2017). DOI: 10.1089/ten.TEC.2017.0033

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Stem cells therapy for naturally occurring intervertebral disc disease - Medical Xpress

Former Tranmere footballer shares powerful picture as he begins fighting cancer with stem cell therapy – Liverpool Echo

Former Tranmere Rovers player Joe Thompson has shared an inspiring photo as he begins stem cell therapy to battle his cancer.

The 28-year-old is battling the disease for the second time, after first discovering tumours in his neck in 2013.

The footballer played 32 games for Rovers in 2012 and 2013, before being diagnosed with nodular sclerosing Hodgkins disease.

He fought through six months of chemotherapy before returning to football, joining Bury and then starting at Rochdale last summer.

Now Joe has shared a brave photo from hospital, as he undergoes stem cell therapy.

Posting the picture to Twitter he said: Little Update, First day of the Stem Cell Harvest Process! Docs are very surprised with how good my blood counts are! Hearts super fit.

When he first announced his cancer had resturned in March Joe said his wife and daughter were his daily motivation.

He said: I will fight this life hurdle with the same belief, courage and desire as my previous battle.

The support shown to me since I discovered my illness has returned has been immense.

I would like to thank my wife, Chantelle, who was my rock in my first encounter and will once again be by my side with the same encouragement, discipline and strength.

Not to mention the love shown to me by both my wife and beautiful daughter Thailula-Lily who are both my motivations daily.

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Former Tranmere footballer shares powerful picture as he begins fighting cancer with stem cell therapy - Liverpool Echo