Epithelial ovarian cancer (EOC) is typically diagnosed at advanced stages of disease, and is characterized by a high rate of relapse after primary surgery and adjuvant chemotherapy. Phase 1 trials at RPCI in patients with EOC with minimal residual disease identified vaccination as a promising strategy to induce immune responses that might delay relapse of disease. While the median time to disease relapse was encouraging in the two trials (19 months and 21 months), the majority of patients developed recurrent disease.
Achieving durable anti-tumor immunity remains a persistent challenge and entails overcoming immunosuppressive responses that limit anti-tumor effector functions. Major obstacles to the development of successful immune strategies include the inability to generate an immune response sufficient to cause tumor rejection and the tumor’s ability to evade immune attack. Induction of immunosuppressive pathways is a major impediment to effective anti-tumor vaccines. Seen in this light, effective immunotherapy requires overcoming pathways that lead to tolerance and tumor escape.
Drs. Brahm Segal, Scott Abrams and Kunle Odunsi are collaborating on research funded by donations to evaluate how immunosuppressive myeloid cells facilitate tumor escape. Their lab has shown that certain populations of peritoneal myeloid cells can suppress stimulated T cell responses. These suppressive cells are observed in both tumor-bearing and non-tumor-bearing lab models.
Since the ovaries are surrounded by peritoneal lining cells, these results point to the local ovarian environment as an immune-privileged site that may impede sustained anti-tumor immunity. Based on these preliminary results, they will test a proof-of-concept approach to modulate the myeloid responses in the EOC environment. Funding from the Alliance grant will enable their team to test whether depletion of specific peritoneal myeloid cells will delay tumor progression and enhance vaccine efficacy in a model of EOC. If successful, this approach will establish the foundation for Phase I clinical studies in patients with EOC.