Immunotherapy is being investigated as a novel treatment for cancer. The Asterias cell therapy platform for cancer immunotherapy aims to stimulate the body's ability to recognize cancer antigens and mount an immune response to control the spread of the disease. Our AST-VAC immunotherapy programs employ three common elements of dendritic cells, telomerase antigen, and the LAMP signal sequence to stimulate robust and specific immune responses to cancer cells (Figure 1).
Figure 1. Key components of the AST-VAC immunotherapy platform.
Stimulates diverse immune responses to extend remission
Universal cancer antigen, conferring proliferative ability
Normal adult cells do not express telomerase, ensuring safety
LAMP enhances antigen presentation by dentritic cells to increase immune response
Licensed from Immunomic Therapeutics
Dendritic cells direct the function of the immune system through the presentation of antigens, and they can be a powerful therapeutic agent when properly directed. We are developing dendritic cell-based vaccines targeting telomerase, a protein expressed in over 95 percent of cancers and rarely found in normal adult cells. Our vaccines also employ the LAMP sequence, licensed from Immunomic Therapeutics, to optimize antigen presentation, increasing immune responses to telomerase.
Our platform includes two distinct approaches to create these vaccines: AST-VAC1, an autologous (patient-specific) vaccine based on cells sourced from the patient, and AST-VAC2, an allogeneic (non-patient specific) vaccine manufactured from our proprietary pluripotent stem cell platform. Both of these programs incorporate the three key elements of dendritic cells, telomerase and LAMP to stimulate immune responses to cancer cells. Additionally, both programs employ numerous improvements designed to improve both immune responses and manufacturability as compared to first generation dendritic cell therapies (Figure 2):
Use of mRNA (vs. peptide pulsing used in other autologous methods) to elicit a broad immune response applicable to a wide range of HLA types
Incorporation of the LAMP targeting sequence to enhance the CD4 (helper/memory) T-cell response
Intradermal injection to gain ready access to lymph nodes,
High concentration (>90%) of mature dendritic cells to maximize immune response
Scalable manufacturing enables the production of multiple doses from a single manufacturing process. In the case of our autologous AST-VAC1 process, sufficient material for 2-3 years of repeat dosing can be made in a single patient-specific process. Our AST-VAC2 program further increases this scalability through the use of our pluripotent stem cell platform for the production of allogeneic dendritic cells for off-the-shelf availability on demand
Cryopreservation of the final product to extend product stability, simplifying logistics
Figure 2. Six differentiating design characteristics differentiate AST-VAC products from first generation DC therapies
In our current clinical programs, each of these approaches has different therapeutic applications in oncology, with near term focus on Acute Myeloid Leukemia (AML) for AST-VAC1 and non-small cell lung cancer (NSCLC) for AST-VAC2. We anticipate that these therapies will be synergistic with other therapies in development for these indications, including new chemotherapeutics and other immunotherapy approaches such as immune checkpoint inhibitors.
To learn more about Asterias pipeline therapies leveraging the immunotherapy platform: