Phase 1 Safety and Feasibility Study of a Personal Neoantigen-Targeting Vaccine in Combination with Immune Checkpoint Blockade in Ovarian Cancer
[Technical Report, Annual Report]
Dana-Farber Cancer Institute
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Although immune checkpoint blockade CPB therapy have demonstrated potent clinical activity across multiple tumor types, only modest effectiveness in ovarian cancer has been observed. In this application, we have proposed a novel treatment approach in epithelial ovarian cancer EOC which consists of administration of neoantigen-targeting vaccines in combination with CPB therapy. We hypothesized that applying this approach to patients with EOC will effectively expand existing tumor-reactive T-cells and broaden the T-cell repertoire to include new tumor-specific T-cells thereby generating highly specific anti-tumor immunity with fewer autoimmune side effects. Throughout the timeline of the award we have proposed to i conduct a clinical trial to determine if NeovaxNivolumab anti-PD-1 antibody is feasible and safe in newly diagnosed or recurrent platinum sensitive EOC, and is associated with evidence of clinical activity ii define the evolution of T cell specificity, state and repertoire following standard of care SOC chemotherapy and after NeovaxNivolumab and iii to characterize the genetic evolution of patient tumor cells and of tumor microenvironment following standard-of-care chemotherapy and after NeovaxNivolumab. We have now obtained HRPO approval and our clinical trial has activated. Relevant to analyses for Aims 2 and 3, we continue to characterize T cell responses and changes in immunogenicity through the course of standard of care chemotherapy. We have already found that standard of care platinum and taxane chemotherapy used in ovarian cancer idoes not deplete T cells although it does deplete granulocytes, ii does not impact the ability of T cells to respond to antigens and iii leads to an increase in TCR diversity.
- Medicine and Medical Research
- Anatomy and Physiology