Abstract 2628: Generation of multi-antigen specific T cells for ovarian cancer using Prussian Blue nanoparticles and photothermal therapy

Abstract

Abstract The immunosuppressive nature of ovarian cancer (OC) allows these tumors to evade the immune system, contributing to late-stage diagnoses and poor clinical outcomes for patients. However, a higher number of tumor-infiltrating lymphocytes is associated with improved clinical outcomes in OC. One type of lymphocyte, the T cell, can traffic to the tumor and kill tumor cells. We have shown that treating tumor cells with Prussian Blue nanoparticles and photothermal therapy (PBNP-PTT) results in immunogenic cell death, a form of cell death that is visible to the immune system, including T cells. PBNP-PTT-treated tumor cells were then used to expand tumor-specific T cells from partially genetically matched healthy donors against breast and brain cancer cell lines. These expanded T cells were better able to recognize and kill the target tumor cell lines than bulk unexpanded T cells from the same donors. Hence, we hypothesized that using PBNP-PTT-treated OC cells would allow us to expand a polyclonal tumor-specific T cell product that is cytolytic against OC cells in vitro and in vivo.We first evaluated whether multi-antigen OC-specific T cells could be expanded from partially genetically matched healthy donors and confirmed that PBNP-PTT elicited immunogenic cell death in the HLA-A*02:01 human OC cell lines Hey and TykNu. Using our established in vitro T cell expansion protocol, we then successfully expanded T cells from multiple HLA-A*02:01 healthy donors (n=3) against these cell lines. Functional analyses—including interferon-gamma ELISPOT, multi-color flow cytometry, and cytotoxicity assays—demonstrated that the expanded T cells had enhanced anti-tumor responses against OC cell lines compared to bulk unexpanded T cells derived from the same donors. Current work is expanding this approach to a syngeneic murine setting in C57BL/6J mice. Moreover, we will evaluate HLA-matched T cells and tumor cells from patients with OC ex vivo. Collectively, these efforts serve as a novel approach towards a curative immunotherapy for OC. Citation Format: Erin E. Grundy, Abigail Lee, Samantha Chin, Melissa Hadley, Danielle Schmidt, Loretta Wang, Olivia Cox, Khadra Omar, Catherine M. Bollard, Rohan Fernandes, Katherine B. Chiappinelli. Generation of multi-antigen specific T cells for ovarian cancer using Prussian Blue nanoparticles and photothermal therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2628.