Th17 immunity is associated with prolonged recurrence-free survival in ovarian cancer. We designed a new strategy to induce ovarian cancer antigen-specific Th17 immunity targeting the folate receptor alpha. Vaccination of ovarian cancer patients resulted in strong durable Th17 and antibody immunity that was associated with prolonged recurrence free survival. Results of the trial and the ongoing Phase II efficacy will be discussed.

Anti-cancer immune responses rely upon the generation of tumor-specific T cells. In particular, response to anti-PD-1 blockade is associated with the presence of exhausted, anti-tumor T cells within the tumor microenvironment (TME). “Immune-ignored” and “T cell-excluded” represent two distinct PD-1 non-response phenotypes. The potential of peripheral and in situ v­­accination to overcome these mechanisms of immunosuppression will be explored and a novel, personalized bacteriophage vaccine platform (ImmunoPhage^TM) will be discussed.

Actranza lab. the latest breakthrough in the delivery of genetic vaccines, including cancer immunotherapy, using Daicel's proprietary pyro-drive jet injection technology, demonstrates  highly sophisticated biphasic injection profiles with an instantaneous jet fluid. This talk will highlight details and advantages on the device and relevant application data.  

An immunogenic colorectal cancer vaccine was used as platform to screen monoclonal antibodies as potential therapeutic candidates. Antibodies were screened against human colorectal cancer cell lines for sensitivity. Those antibodies that met these criteria were selected for tumor specificity as well as antitumor activity. Two novel monoclonal antibodies that met these criteria have been further characterized for function. The antibodies were also used to identify the antigenic target they recognize. The lead candidate, Ensituximab, has recently completed a Phase 2 trial in chemotherapy refractory colorectal cancer. Correlative studies were performed in the laboratory demonstrating enhancement of antitumor activity when combined with cytokine therapy. A Ph2b study is currently planned with this combination approach. In addition, a second novel monoclonal antibody, NEO-201 with a different tumor target and various mechanisms of action is currently in clinical trials. Combination approaches are currently being studied based on these mechanisms with Ph2 studies planned in a variety of tumors that express its target.

In an initial phase 1b trial, we demonstrated that neoantigen vaccination can generate neoepitope-specific CD4+ and CD8+ T cells in glioblastoma, an immunologically “cold” tumor with low mutational burden. Of note, concurrent corticosteroids abrogated vaccine induced immune responses. Finally, we confirmed that neoepitope-specific T cells can successfully traffic into intracranial GBM tumors. Updates on strategies to optimize our neoantigen approach and enhance its efficacy via combinatorial regimens will be reviewed.

Tumor genomics guided advances in precision medicine and T-cell mediated immunotherapy have changed the paradigm for treatment in many cancer settings. More recently, the observation that somatic changes in tumor genomes lead to tumor neoantigens that can be recognized by the immune system has added yet another dimension to tumor genomics guided personalized treatments. The presentation discusses the design and clinical implementation of DNA encoded neoantigen targeted personalized immunotherapies.