Integrating Cancer Vaccines in the Standard-of-Care of Ovarian Cancer: Translating Preclinical Models to Human

Abstract

As the majority of ovarian cancer (OC) patients are diagnosed with metastatic disease, less than 40% will survive past 5 years after diagnosis. OC is characterized by a succession of remissions and recurrences. The most promising time point for immunotherapeutic interventions in OC is following debulking surgery. Accumulating evidence shows that T cells are important in OC; thus, cancer vaccines capable of eliciting antitumor T cells will be effective in OC treatment. In this review, we discuss different cancer vaccines and propose strategies for their incorporation into the OC standard-of-care regimens. Using the murine ID8 ovarian tumor model, we provide evidence that a cancer vaccine can be effectively combined with OC standard-of-care to achieve greater overall efficacy. We demonstrate several important similarities between the ID8 model and OC patients, in terms of response to immunotherapies, and the ID8 model can be an important tool for evaluating combinatorial regimens and clinical trial designs in OC. Other emerging models, including patient-derived xenograft and genetically engineered mouse models, are continuing to improve and can be useful for evaluating cancer vaccination therapies in the near future. Here, we provide a comprehensive review of the completed and current clinical trials evaluating cancer vaccines in OC.

Single CAR-T cell treatment controls disseminated ovarian cancer in a syngeneic mouse model

“…Combination with oncolytic viruses for induction of innate and natural killer cell responses 47 48 and vaccines that elicit endogenous T-cell activity could be key combination therapies to sustain tumor control, without the emergence of CAR-antigen loss variants. [49][50][51][52] There is some evidence that endogenous T cells can be recruited in the ID8 tumor model, 50 53 but their existence in the ID8 CAR system described here remains to be seen. Nevertheless, our findings using a single dose of CAR T-cells are even more notable given that other strategies would likely provide greater benefit through synthetic engineering, recipient T cell selections, or combination treatments.…”

Immunologic Signatures of Peripheral Blood T Cells Reveal the Outcome of p53MVA Vaccine and Pembrolizumab Treatment in Patients with Advanced Ovarian Cancer

“…Immunotherapy for the treatment of ovarian cancer remains controversial ( 2 ). Early observations that intratumoral T-cell infiltration is associated with better survival led to the hypothesis that ovarian cancer is immunogenic and potentially responsive to immunotherapy ( 3 ). Challenging this hypothesis is a recent observation that the tumor mutational burden, which correlates with the number of neoantigens, is in the lower end of spectrum for ovarian cancer with only 1–3.5 mutations/Mb (immunogenic melanoma has 14–47 mutations/Mb).…”