A first of its kind treatment vaccine has moved into a phase I clinical trial for patients with non-small cell lung cancer (NSCLC), under a collaboration agreement between Cancer Research UK and Asterias Biotherapeutics Inc.
Cancer Research UK will manage the initial clinical development of AST-VAC2, a promising immunotherapy candidate derived from a standardised human embryonic stem cell line, which was brought to the charity through its Clinical Development Partnerships (CDP) scheme.
If shown to be safe and effective, it’s hoped that AST-VAC2 could be used as an additional treatment for patients who no longer have advanced disease but whose lung cancer is at high risk of coming back, or in combination with other treatments for patients with advanced disease.
Dr Nigel Blackburn, Cancer Research UK’s director of drug development, said: “This vaccine trial is a pioneering approach to improving treatment for lung cancer, the biggest cause of cancer death worldwide.
“By coupling our expertise with a leading biotechnology company, we’ve accelerated the development of this experimental treatment by years.”
The vaccine is made from dendritic cells that are able to kick-start the body’s immune system. They present molecules called antigens on their surface and orchestrate a T-cell immune response against cells bearing the same antigens.
AST-VAC2 dendritic cells are engineered to express a modified form of a protein called telomerase, which is almost always present at high levels in various types of cancer cells, but rarely found in healthy cells.
This modified form of telomerase, called hTERT, can stimulate a natural immune response targeted at cancer cells. High levels of telomerase are a common feature of many cancers, so AST-VAC2 has the potential to become an immunotherapy option for other types of cancer beyond NSCLC.
Previous dendritic cell therapies have been made using patients’ own cells, but this process is costly, slow and inefficient. By using a pioneering approach of growing mature dendritic cells from a single human embryonic stem cell line in the laboratory, it’s hoped AST-VAC2 will overcome these challenges.
Under the agreement, Asterias transferred its innovative cell therapy manufacturing process to Cancer Research UK. The charity’s Biotherapeutics Development Unit then developed and qualified the process ready for manufacture in its own GMP (Good Manufacturing Practice) manufacturing facility.
Cancer Research UK’s Centre for Drug Development will now take AST- VAC2 through a Phase I clinical trial in NSCLC.*
This trial will demonstrate the feasibility of the manufacturing process at a clinical scale as well as testing whether it’s a safe and effective** treatment for patients with NSCLC. Researchers will test blood samples taken at various time points to assess whether the patient’s immune system is capable of mounting an immune response against hTERT.
Professor Christian Ottensmeier, chief investigator for the trial and head of the Southampton Experimental Cancer Medicines Centre (ECMC), said: “Vaccines that boost the immune system to recognise and fight cancer could become a routine part of treatment for certain patients in the future, but we need to make them cheaper and easier to produce.
“With its potential to be used off-the-shelf, AST-VAC2 is an exciting development in the rapidly evolving field of immunotherapy.”
Michael Mulroy, president and chief executive officer of Asterias Biotherapeutics Inc, said: “The experience and expertise of Cancer Research UK’s Centre for Drug Development and Biotherapeutics Development Unit have brought us a step closer to realising the clinical potential of this exciting experimental treatment. We appreciate the efforts of Cancer Research UK and want to thank the organization for moving this experimental treatment into clinical development.
“In the future, there’s also the potential to utilise this novel platform technology to produce treatments that could, in theory, target multiple tumour antigens and thereby treat a whole range of different cancers and tumour types.”
Cancer Research UK’s commercial activity operates through Cancer Research Technology Ltd. (CRT), a wholly owned subsidiary of Cancer Research UK. It is the legal entity which pursues drug discovery research in themed alliance partnerships and delivers varied commercial partnering arrangements.
*The trial is open to patients who are HLA2+ with advanced NSCLC (metastatic or locally advanced disease) in the first instance, with the expansion phase open to patients who are HLA A2+ and disease free after treatment for NSCLC.
**Efficacy of AST-VAC2 will be assessed by 2-year overall survival, time to relapse and measurement of immune response.
Experimental Cancer Medicine Centres are jointly funded by Cancer Research UK, the National Institute for Health Research in England and the Departments of Health for Scotland, Wales and Northern Ireland.
About Cancer Research UK’s Clinical Development Partnerships
CDP is a Cancer Research UK initiative that aims to develop promising anti-cancer agents from companies that are not able to take them through early phase clinical trials themselves. Under the scheme, Cancer Research UK sponsors and funds early clinical development, while companies retain all underlying rights to their programmes. At the end of the study, companies can decide if they wish to develop the drug further based on the clinical trial results. If they choose not to, the charity may secure an alternative partner and ensure the drug has every possible chance of reaching patients, with a share of future income returned to Cancer Research UK.
About Cancer Research UK’s Centre for Drug Development
Cancer Research UK has an impressive record of developing novel treatments for cancer. The Cancer Research UK Centre for Drug Development, formerly the Drug Development Office, has been pioneering the development of new cancer treatments for 25 years, taking over 140 potential new anti-cancer agents into clinical trials in patients. It currently has a portfolio of around 30 new anti-cancer agents in preclinical development, Phase I or early Phase II clinical trials. Six of these new agents have made it to market including temozolomide for brain cancer, abiraterone for prostate cancer and rucaparib for ovarian cancer. Two other drugs are in late development Phase III trials. This rate of success is comparable to that of any pharmaceutical company.
About Asterias Biotherapeutics
Asterias Biotherapeutics, Inc. is a biotechnology company dedicated to developing cell-based therapeutics to treat neurological conditions associated with de-myelination and cellular immunotherapies to treat cancer. 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-VAC2 (antigen-presenting allogeneic dendritic cells) represents a second generation, allogeneic cancer immunotherapy that also targets telomerase presenting tumor cells. The company’s research partner, Cancer Research UK, has recently commenced a first-in-human (FIH) clinical trial of AST-VAC2 in non-small cell lung cancer. AST-VAC1 (antigen-presenting autologous dendritic cells) is an autologous cancer immunotherapy targeting telomerase presenting tumor cells, with promising efficacy and safety data from a Phase 2 study in Acute Myeloid Leukemia (AML) which the company believes is proof of concept data for AST-VAC2. Additional information about Asterias can be found at www.asteriasbiotherapeutics.com.