Toca 511 & Toca FC has a dual mechanism of action within the tumor microenvironment: In addition to the direct killing of Toca 511-infected cancer cells, 5-FU can kill neighboring uninfected cancer cells and immune-suppressive myeloid cells, including myeloid-derived suppressor cells, or MDSCs, as well as tumor associated macrophages, or TAMs. Cancer cell death releases damage-associated molecular patterns, or DAMPs, pathogen-associated molecular patterns, or PAMPs, and cancer associated antigens, resulting in antigen presentation and activation of T cells. Such cancer cell killing leads to the release of cancer associated antigens and local inflammatory DAMPs and PAMPs, which stimulate the antigen-presenting cells in the tumor micro-environment to present the cancer associated-antigens to the CD4 (helper) and CD8 (killer) T cells of the immune system. This results in further induction and harnessing of these cells against the cancer associated antigens to kill more cancer cells and provide durable control of the cancer, a process called acquired immunity. This approach is designed to selectively destroy cancer cells within the body, while leaving healthy cells unharmed.
Based on preclinical data, we believe Toca 511 & Toca FC may have therapeutic benefit in multiple solid tumor cancers. Tocagen initiated a Phase 1b clinical trial for the treatment of metastatic colorectal, pancreatic, breast, lung, melanoma and renal cancers, all of which can all spread to the brain and other organs. Because Toca 511 & Toca FC has been well tolerated in clinical trials to date, Tocagen believes it could be added to established cancer treatments without additional toxicity.