Cancer Research UK, the world’s leading cancer charity dedicated to saving lives through research, and Cancer Research Technology (CRT), the charity’s development and commercialisation arm, have reached an agreement with Asterias Biotherapeutics, Inc, a biotechnology company in the emerging field of regenerative medicine, to take forward Asterias’ novel immunotherapy treatment AST-VAC2 into clinical trials in subjects with non-small cell lung cancer.

AST-VAC2 represents the tenth treatment to enter Cancer Research UK’s Clinical Development Partnerships (CDP) scheme, with six having progressed into the clinic to date. CDP is a joint initiative between Cancer Research UK’s Drug Development Office (DDO) and Cancer Research Technology, to develop promising anti-cancer agents which pharmaceutical companies do not have the resources to progress through early phase clinical trials.

AST-VAC2 is a non-patient specific (allogeneic) cancer vaccine designed to stimulate patients’ immune systems to attack telomerase, a protein that is expressed in over 95 per cent of cancers but is rarely expressed in normal adult cells.

The vaccine was developed following successful early phase clinical trials of a similar, patient specific (autologous) Asterias vaccine, called AST-VAC1, which was derived from patients’ blood cells and tested in prostate cancer and acute myeloid leukaemia.

Unlike AST-VAC1, and other autologous (patient specific) vaccines that are developed from a patient’s own cells, AST-VAC2 is derived from human embryonic stem cells (hESCs), meaning it can be produced on a large scale and stored ready for use, rather than having to produce a specific version of the drug for each patient.

The trial of AST-VAC2 will evaluate the safety and toxicity of the vaccine, feasibility, stimulation of patient immune responses to telomerase and AST-VAC2, and clinical outcome after AST-VAC2 administration in patients with resected early-stage lung cancer and in patients with advanced forms of the disease.

Pedro Lichtinger, Asterias’ chief executive officer, said: “The Asterias collaboration with Cancer Research UK’s Drug Development Office and CRT represents a major step in advancing our proprietary dendritic cell platform for the potential benefit of patients.

“AST-VAC2 is based on a specific mode of action that is complementary and potentially synergistic to other immune therapies. We are delighted to partner with Cancer Research UK to advance this important platform through phase 1/2 clinical trials.  Cancer Research UK’s Drug Development Office has the global recognition of having the quality, capability and track record of successfully advancing development programmes.  We are excited about the possibility of favorably impacting the lives of patients across multiple cancers and are proud to be working with Cancer Research UK.”

Under the agreement, Asterias will complete development of the manufacturing process for AST-VAC2. Cancer Research UK will then produce the vaccine and conduct the phase 1/2 clinical trial in the UK. On completion of the clinical trial, Asterias will have an exclusive first option to acquire a license to the data from the trial on pre-agreed terms including an upfront payment, milestones and royalties on sales of products. If Asterias declines this option, CRT will then have an option to obtain a license to Asterias’ intellectual property to continue the development and commercialisation of AST-VAC2 and related products in exchange for a revenue share to Asterias of development and partnering proceeds.

Dr. Jane Lebkowski, president of research and development at Asterias, said: “The use of human embryonic stem cells to derive allogeneic dendritic cells for cancer immunotherapy has the potential to dramatically improve the scalability, consistency, and feasibility of cellular cancer vaccines.  We believe this collaboration will enable the acceleration of clinical studies of AST-VAC2 and the collection of important proof-of-concept data for the entire human embryonic stem cell-derived dendritic cell immunotherapy platform.”

Nigel Blackburn, Cancer Research UK’s director of drug development, said: “Recent advances in cancer immunotherapy have demonstrated the exciting potential of these treatments to improve outcomes in devastating diseases such as lung cancer. Better treatment options for lung cancer are badly needed and it is through collaborations such as this that we can save more lives sooner.”

Vaccines have the potential to act synergistically with immune checkpoint inhibitors by using the checkpoint inhibitor to activate, and the vaccine to direct, the immune response to cancer cells.  One promising cancer vaccine approach uses dendritic cells, which normally serve this training function – known as antigen presentation – in the human immune system.  However, first generation dendritic cell vaccines, such as Dendreon’s Provenge® (sipuleucel-T) and Asterias’ AST-VAC1, must be manufactured on a patient-by-patient (autologous) basis, which can result in higher costs of manufacture, variability in product performance, and delayed availability of such autologous products.   Asterias’ AST-VAC2 product represents a scalable platform for low cost, consistent manufacturing of a dendritic cell vaccine with on demand availability.

AST-VAC2 is an immunotherapeutic product candidate consisting of human embryonic stem cell derived- mature dendritic cells (hESC-DCs) that are engineered to express telomerase.  AST-VAC2 is designed as an “off-the-shelf” vaccine platform to stimulate an immune response against tumor cells expressing telomerase.  Telomerase is expressed in most human cancers, and plays an important role in the prolonged proliferative lifespan of cancer cells.  In contrast, telomerase expression is rare and transient in most normal adult tissues, making telomerase an attractive target for cancer immunotherapy.

Previous studies of a patient specific (autologous), peripheral blood-derived, dendritic cell vaccine targeting telomerase (AST-VAC1) in prostate cancer and acute myelogenous leukemia (AML) provided promising data supporting the safety and feasibility of dendritic cell-based telomerase immunotherapy, and showed telomerase-specific immune responses in 55% of AML and 95% of prostate cancer patients.

Additionally, in the AST-VAC1 prostate cancer trials, reductions in PSA velocity and circulating tumor cells which correlated with patient immune responses were observed. The use of human embryonic stem cells, as opposed to patient blood, as the starting material for production of AST-VAC2 provides a scalable system for the production of a large number of vaccine doses in a single production lot, enabling reduced costs of manufacturing, “off-the-shelf” availability, and improved product consistency compared to autologous dendritic cell immunotherapy products.

Asterias’ core technologies center on stem cells capable of becoming all of the cell types in the human body, a property called pluripotency.

Cancer Research Technology (CRT) is a specialist commercialisation and development company, which aims to develop new discoveries in cancer research for the benefit of cancer patients. CRT works closely with leading international cancer scientists and their institutes to protect intellectual property arising from their research and to establish links with commercial partners.