Aspirin Prevents Platelets from Suppressing Anticancer T Cells – Genetic Engineering & Biotechnology News (blog)

Platelets do more than promote clotting. They weaken one of the bodys immune defenses against cancer. Unfortunately, platelets tend to work against the immuno-oncology treatments that try to strengthen T-cell attacks on cancer.

Platelets, new research indicates, suppress T-cell immunity against cancer by expressing a transmembrane protein, the glycoprotein A repetitions predominant (GARP) receptor. Platelet GARP can snag a growth factor, transforming growth factor- (TGF), and thereby promote cancer. When GARP binds with TGF, the latter can become activated and then convert effector T cells, which normally attack cancer with an inflammatory reaction, into regulatory (suppressor) T cells, which turn off the inflammatory reaction.

The new findings appeared May 5 in the journal Science Immunology, in an article entitled Platelets Subvert T Cell Immunity against Cancer via GARP-TGF Axis. This study expands on earlier findings that indicated platelets, in cancer-associated thrombocytosis, might make cancer worse.

An unbiased biochemical and structural biology approach established TGF and lactate as major platelet-derived soluble factors to obliterate CD4+ and CD8+ T cell functions, wrote the articles authors. Moreover, we found that platelets are the dominant source of functional TGF systemically as well as in the tumor microenvironment through constitutive expression of the TGF-docking receptor GARP rather than secretion of TGF per se.

Scientists have known for several years that certain cancers suppress T cells to avoid the immune system. That is why adoptive T-cell therapy is one of the most promising advances in modern cancer treatment. It is a type of immunotherapy that awakens the immune system by retraining a patient's T cells to recognize their cancer. T cells are isolated from a patient's blood and retrained, or "primed," to recognize tumor cells. They are then injected back into the patient's bloodstream where they can now hunt and fight cancer.

In the current study, scientists have shown that genetic targeting of platelets enhances adoptive T-cell therapy of cancer. Platelet-specific deletion of the GARP-encoding gene Lrrc32, the authors of the Science Immunology article indicated, blunted TGF activity at the tumor site and potentiated protective immunity against both melanoma and colon cancer.

This work, which was carried out by scientists based at the Medical University of South Carolina, revealed the mechanism behind platelets activation of TGF. The scientists showed that in genetically modified mice without GARP, the molecular hook on the surface of platelets, adoptive T-cell therapy was more successful at controlling melanoma. This meant that platelets without the ability to grab and activate TGF were not able to suppress cancer-fighting T cells. Similar experiments confirmed this result in mice with colon carcinoma.

Finally, mice with normal platelets that were given melanoma and then adoptive T-cell therapy survived longer and relapsed less when aspirin and clopidogrel, two antiplatelet drugs, were added. The researchers noted that antiplatelet drugs by themselves were not successful in combating melanoma in their experiments.

This study could inform future treatment of melanoma and other cancers and offers a sound reason to test antiplatelet drugs in clinical trials of adoptive T-cell therapy. In patients with melanoma or other cancers, adoptive T-cell therapy may be successful if highly available platelet-blocking drugs such as aspirin are added to the treatment. However, the current standard of care for melanoma is not adoptive T-cell therapy, but rather so-called checkpoint inhibitors.

The team at the Medical University of South Carolina, which was led by Zihai Li, M.D., Ph.D., want to know if combination therapy with antiplatelet drugs could improve existing cancer treatment. They are waiting for approval to begin a clinical trial that will test certain checkpoint inhibitors in combination with aspirin and clopidogrel for the treatment of patients with advanced cancers. Dr. Li's trial will complement clinical trials that are already testing adoptive T-cell therapy as a single treatment for cancer.

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

See original here:
Aspirin Prevents Platelets from Suppressing Anticancer T Cells - Genetic Engineering & Biotechnology News (blog)

Presidential Symposium at the American Society of Gene and Cell Therapy (ASGCT) 20th Annual Meeting Will Feature … – Yahoo Finance

FREMONT, Calif., May 3, 2017 /PRNewswire/ --Asterias Biotherapeutics, Inc. (NYSE MKT: AST), a biotechnology company pioneering the field of regenerative medicine, today announced that data from its AST-OPC1 clinical program for severe cervical spinal cord injury will be presented during the Presidential Symposium at the American Society of Gene and Cell Therapy (ASGCT) 20th Annual Meeting, being held in Washington, D.C. during May 10-13, 2017.

"The ASGCT decision to include a presentation on AST-OPC1 in its Presidential Symposium signifies the ground-breaking nature of our program, and reflects the encouraging efficacy and safety data we have seen to date in patients with severe spinal cord injuries that have been treated with AST-OPC1," said Steve Cartt, President and Chief Executive Officer of Asterias. "Data will be presented from our SCiStar study demonstrating the potential of AST-OPC1 to help patients with complete paralysis regain increased arm, hand and finger function, and thus greater ability to live independently."

Jane S. Lebkowski, Ph.D., Asterias' President of R&D and Chief Scientific Officer, will be one of the presenters during the Presidential Symposium session scheduled on Friday, May 12, 2017 at 1:00pm Eastern Time. Dr. Lebkowski's presentation, titled "498 - Safety and Efficacy of Human Embryonic Stem Cell Derived Oligodendrocyte Progenitor Cells (AST-OPC1) in Patients with Subacute Cervical Spinal Cord Injury," is expected to begin at 2:15pm Eastern Time. The abstract for Dr. Lebkowski's presentation at the ASGCT meeting is available online at: http://www.abstractsonline.com/pp8/#!/4399/presentation/1996.

ASGCT is the primary professional membership organization for gene and cell therapy. The Society's members are scientists, physicians, patient advocates, and other professionals. Its members work in a wide range of settings including universities, hospitals, government agencies, foundations, biotechnology and pharmaceutical companies. Its mission is to advance knowledge, awareness, and education leading to the discovery and clinical application of gene and cell therapies to alleviate human disease.

About the SCiStar Trial

The SCiStar trial is an open-label, single-arm trial testing three sequential escalating doses of AST-OPC1 administered at up to 20 million AST-OPC1 cells in as many as 35 patients with sub-acute, C-5 to C-7, motor complete (AIS-A or AIS-B) cervical SCI. These individuals have essentially lost all movement below their injury site and experience severe paralysis of the upper and lower limbs. AIS-A patients have lost all motor and sensory function below their injury site, while AIS-B patients have lost all motor function but may retain some minimal sensory function below their injury site. AST-OPC1 is being administered 14 to 30 days post-injury. Patients will be followed by neurological exams and imaging procedures to assess the safety and activity of the product.

The study is being conducted at six centers in the U.S. and the company plans to increase this to up to 12 sites to accommodate the expanded patient enrollment. Clinical sites involved in the study include the Medical College of Wisconsin in Milwaukee, Shepherd Medical Center in Atlanta, University of Southern California (USC) jointly with Rancho Los Amigos National Rehabilitation Center in Los Angeles, Indiana University, Rush University Medical Center in Chicago and Santa Clara Valley Medical Center in San Jose jointly with Stanford University.

Asterias has received a Strategic Partnerships Award grant from the California Institute for Regenerative Medicine, which provides $14.3 million of non-dilutive funding for the Phase 1/2a clinical trial and other product development activities for AST-OPC1.

Additional information on the Phase 1/2a trial, including trial sites, can be found at http://www.clinicaltrials.gov, using Identifier NCT02302157, and at the SCiStar Study Website (www.SCiStar-study.com).

About AST-OPC1

AST-OPC1, an oligodendrocyte progenitor population derived from human embryonic stem cells, has been shown in animals and in vitro to have three potentially reparative functions that address the complex pathologies observed at the injury site of a spinal cord injury. These activities of AST-OPC1 include production of neurotrophic factors, stimulation of vascularization, and induction of remyelination of denuded axons, all of which are critical for survival, regrowth and conduction of nerve impulses through axons at the injury site. In preclinical animal testing, AST-OPC1 administration led to remyelination of axons, improved hindlimb and forelimb locomotor function, dramatic reductions in injury-related cavitation and significant preservation of myelinated axons traversing the injury site.

Read More

In a previous Phase 1 clinical trial, five patients with neurologically complete, thoracic spinal cord injury were administered two million AST-OPC1 cells at the spinal cord injury site 7-14 days post-injury. They also received low levels of immunosuppression for the next 60 days. Delivery of AST-OPC1 was successful in all five subjects with no serious adverse events associated with AST-OPC1. No evidence of rejection of AST-OPC1 was observed in detailed immune response monitoring of all patients. In four of the five patients, serial MRI scans indicated that reduced spinal cord cavitation may have occurred. Based on the results of this study, Asterias received clearance from FDA to progress testing of AST-OPC1 to patients with cervical spine injuries, which represents the first targeted population for registration trials.

About Asterias Biotherapeutics

Asterias Biotherapeutics, Inc. is a biotechnology company pioneering the field of regenerative medicine. The company's proprietary cell therapy programs are based on its pluripotent stem cell and immunotherapy platform technologies. Asterias is presently focused on advancing three clinical-stage programs which have the potential to address areas of very high unmet medical need in the fields of neurology and oncology. AST-OPC1 (oligodendrocyte progenitor cells) is currently in a Phase 1/2a dose escalation clinical trial in spinal cord injury. AST-VAC1 (antigen-presenting autologous dendritic cells) is undergoing continuing development by Asterias based on promising efficacy and safety data from a Phase 2 study in Acute Myeloid Leukemia (AML), with current efforts focused on streamlining and modernizing the manufacturing process. AST-VAC2 (antigen-presenting allogeneic dendritic cells) represents a second generation, allogeneic cancer immunotherapy. The company's research partner, Cancer Research UK, plans to begin a Phase 1/2a clinical trial of AST-VAC2 in non-small cell lung cancer in 2017. Additional information about Asterias can be found at http://www.asteriasbiotherapeutics.com.

FORWARD-LOOKING STATEMENTS

Statements pertaining to future financial and/or operating and/or clinical research results, future growth in research, technology, clinical development, and potential opportunities for Asterias, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "believes," "plans," "anticipates," "expects," "estimates") should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products, uncertainty in the results of clinical trials or regulatory approvals, need and ability to obtain future capital, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the businesses of Asterias, particularly those mentioned in the cautionary statements found in Asterias' filings with the Securities and Exchange Commission. Asterias disclaims any intent or obligation to update these forward-looking statements.

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/presidential-symposium-at-the-american-society-of-gene-and-cell-therapy-asgct-20th-annual-meeting-will-feature-presentation-on-asterias-ast-opc1-for-spinal-cord-injury-300450272.html

Continued here:
Presidential Symposium at the American Society of Gene and Cell Therapy (ASGCT) 20th Annual Meeting Will Feature ... - Yahoo Finance

Platelets suppress T cell immunity against cancer – Science Daily

Platelets suppress T cell immunity against cancer Science Daily Scientists have known for several years that certain cancers suppress T cells to avoid the immune system. That is why adoptive T cell therapy is one of the most promising advances in modern cancer treatment. It is a type of immunotherapy that awakens ...

Read the original:
Platelets suppress T cell immunity against cancer - Science Daily

CAR T Cells: Keeping Pace With Adverse Effects of an Emerging Therapy – Oncology Nurse Advisor

Oncology Nurse Advisor

CAR T Cells: Keeping Pace With Adverse Effects of an Emerging Therapy Oncology Nurse Advisor Chimeric antigen receptor T cells (CAR T cells) are human T cells that are collected from the patient and genetically modified to express a CAR immunoreceptor. The modified CAR T cells target specific surface proteins on cancer cells. CAR T cell ...

Go here to read the rest:
CAR T Cells: Keeping Pace With Adverse Effects of an Emerging Therapy - Oncology Nurse Advisor

University of Suffolk begins link with UK Stem Cell Bank for science courses – East Anglian Daily Times

PUBLISHED: 13:11 05 May 2017 | UPDATED: 13:23 05 May 2017

Jason Noble

University of Suffolk main building

Archant

Email this article to a friend

To send a link to this page you must be logged in.

The department for science and technology at the university recently began the collaboration with the aim of ensuring that the MSc Regenerative Medicine and BSc (Hons) Bioscience courses are informed by high-standards in the industry.

The tie-up will also mean a boost for research into regenerative medicine and stem cell use at the university.

Dr Federica Masieri, senior lecturer and course leader for MSc Regenerative Medicine said: We are delighted to be collaborating with what is considered one of the most reputable bodies in the field of stem cell industry.

It is recognised that employers in the regenerative medicine industry require graduates and postgraduates equipped with the most up to date skills, to ensure a seamless assimilation in the constantly evolving stem cellrelated work environment.

This collaboration will help us ensure our students are trained in line with requirements of such employers, by reviewing and developing courses as informed by the standards applied at UKSCB.

To launch the joint scheme, final year students paid a visit to the stem cell bank in London to help the students understand the logistics and complexities of the work there, as well as lectures from leading figures at the leading institution.

The university is aiming to make the trip an annual visit for final year students.

Dr Masieri said: A career in life science is a busy, fast-evolving and challenging one. It makes it an exciting area of endeavour, however there is a constant need to keep up with the rapid pace of change.

By establishing this relationship we are better placed to do this, at par with well-established universities with many years of history in the industry.

Prof Glyn Stacey, director of UKSCB added: The UKSCB is committed to advancing scientific research; we welcome the opportunity to educate, train and inspire the next generation of scientists.

Moreover finalisation of agreements are underway which could see MSc student placements with the UKSCB.

Read this article:
University of Suffolk begins link with UK Stem Cell Bank for science courses - East Anglian Daily Times

BioNews – Unproven stem cell therapies promise versus evidence – BioNews

The ability of stem cells to divide into different mature cell types has ignited the field of regenerative medicine. Stem cells promise to repair and regenerate damaged or diseased tissues without the need for orthodox medical or surgical interventions.

However, there is disparity between the expectations held by the general public and some medical professionals versus the reality of the emerging clinical evidence. This disconnect was highlighted recently by the case of three elderly patients who were blinded by the use of an unproven stem cell therapy at a clinic in Florida, USA (BioNews 893).

While stem cell therapies in the field of haematology are showing promise, there are still many challenges in using them in any other disease models. In some countries, medical professionals are using unproven stem cell therapies as medical procedures to treat patients in lieu of conventional treatment pathways. What is more, these practitioners are operating under the premise of a trial.

Proponents of using stem cell therapies outside the context of a true clinical trial believe that these therapies are inherently safe, particularly if the stem cells derive from the individual patient themselves. And the medical professionals offering unproven stem cell therapies are convinced that the potential benefits of undergoing the therapy far outweigh the potential risks.

These benefits are used as an argument to forge ahead with unproven therapies outside ofclinical trials, as regulatory bodies are often to slow to regulate for the fast-paced field of regenerative medicine;gaining regulatory approval is usually a lengthy and costly process. And the regulation that is in place is often narrow in scope and does not account for the variety of products and manipulative techniques used in the field.

An anecdotal account of a stem cell therapys potential to cure a disease, however, does not make for an adequate standard of evidence. In the Florida case, three elderly patients with a progressive eye disease sought out an unproven stem cell therapy. The clinic involved was offering the therapy under the guise of a trial, however the patients had to pay for the procedure (in itself a 'red flag') that promised to 'cure' their disease. The therapy not only failed, but all three patients are now blind as described in The New England Journal of Medicine on 16 March.

Referring back to the disparity in expectations, how the word 'trial' is understood helps to clarify the basis of thedisconnect between the public and clinicians, and emerging evidence. The word 'trial' in the sense of a clinical trial calls for a robust experimental framework and sets of regulations and standards that safeguard the enrolled patients' rights and overall health. Furthermore, trials are performed in a phased manner to ensure any potential risks are minimised. The results generated from a certain phase informs the researchers as to the most effective way to proceed or indeed not proceed.

Using the word 'trial' in the sense of administering a therapy outside of the setting described above, however, only truly refers to the inherent risk of the therapy not working. Moreover, when being administered by a trusted medical professional, the harms of the therapy are often overshadowed by the promise of a'cure' relayed bythese professionals.

The differences in the interpretation of the word trial among medical professionals is reflected by the lack of strict regulation among professional bodies, such as medical councils and regulatory bodies including the Food & Drug Administration (FDA). While the FDA, for example, has published more specific guidelines in October 2015, these are unenforceable on a global scale.

Interestingly, on a regulatory level, there are opportunities afforded to medical professionals to use unproven stem cell therapies outside the context of a clinical trial as noted in the International Society for Stem Cell Research (ISSCR) 2016 guidelines:

...the ISSCR acknowledges that in some very limited cases, clinicians may be justified in attempting medically innovative stem cell-based interventions in a small number of seriously ill patients.

However the ISSCR goes on to clarify that it 'condemns' the use of unproven stem cell therapies in any other setting where clinical need is not deemed serious.

In relation to classifying unproven stem cell therapies as a medical procedure, the 2014 United States of America v Regenerative Sciences, LLC et al case dealt with the use of mesenchymal stem cells taken from a sample of a patient's own bone marrow to treat their own orthopaedic disorders. In this case, the court was not convinced that manipulating stem cells outside the body and reintroducing them to the patient was a matter of standard 'medical procedure', as argued by the companyRegenerative Sciences LLC. Instead, the court upheld the FDAs right to regulate the manufacturing (or manipulating) of these stem cells: however cases where there is significantly less manipulation of stem cells are yet to be tested.

Issues remain regarding how best to regulate the use of stem cell therapies, particularly in the early phases of their development. There have been calls for strict regulation through bodies such as the FDA, but others argue that strict regulation will only curtail the benefits stem cell therapies can impart. On the other hand, regulations that are too lenient, it is argued, will only harm the patient seeking the therapy, as a solid evidence base will not yet have been compiled for the therapy.

See the original post here:
BioNews - Unproven stem cell therapies promise versus evidence - BioNews