Abstract IA20: Personalized whole-tumor antigen vaccines in ovarian cancer: Using tumors for therapy

Abstract

Abstract Disappointing results have been observed with the first-generation therapeutic cancer vaccines. However, the renaissance of immunotherapy with the checkpoint inhibitors and the demonstration, in preclinical models, that personalized vaccines can induce efficient antitumor T-cell responses have led to a renewed interest in cancer vaccination. Personalized whole-tumor lysate vaccines can encompass all putative antigens in a patient’s tumor and can potentially induce a broader, more efficient immune response. We report here a clinical study utilizing a personalized vaccine generated by autologous dendritic cells (DC) pulsed with autologous whole-tumor cell lysate (OCDC), in platinum-treated, immunotherapy-naïve, recurrent ovarian cancer patients in combination with bevacizumab or bevacizumab plus low-dose intravenous cyclophosphamide until disease progression or vaccine exhaustion. A total of 392 vaccine doses were administered without serious adverse events. Vaccine was shown to induce T-cell responses to autologous tumor antigen, which were associated with significantly prolonged survival (PFS). Vaccine was also shown to amplify T-cell responses against mutated neoepitopes derived from nonsynonymous somatic tumor mutations, and this included priming of T cells against previously unrecognized neoepitopes as well as novel T-cell clones of markedly higher avidity against previously recognized neoepitopes. Importantly, we demonstrate that the median PFS was 11.1 months in the population receiving the combination of vaccine plus bevacizumab and low-dose cyclophosphamide as compared to only 4.1 months in a historic population of patients from the same institution who received standard bevacizumab and low-dose cyclophosphamide without vaccine. We also demonstrate that survival at 2 years was 100% in the vaccine plus bevacizumab/cyclophosphamide group while it was only 40% in control patients receiving bevacizumab and cyclophosphamide alone. This proof-of-concept clinical study gives us a new horizon for the application of whole-tumor lysate personalized vaccines. Citation Format: Lana E. Kandalaft. Personalized whole-tumor antigen vaccines in ovarian cancer: Using tumors for therapy [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr IA20.