Concomitant Treatment of Tumor Treating Fields (TTFields) with Neoantigen-Targeted Anticancer Vaccines to Effectively Treat Murine Pancreatic Tumors
Abstract
Purpose
Tumor-treating-fields (TTFields) therapy uses alternating electric fields delivered via transducer arrays placed regionally close to the tumor site to non-invasively inhibit tumor growth. Although important insights into the mechanisms underlying the anticancer effects of TTFields in-vivo have been identified, further investigation is needed. One hypothesis is that TTFields therapy enhances tumor immunogenicity. The overall goal of this study is to determine whether TTFields alone or concomitantly-treated with a neoantigen targeted vaccine, PancVax, can stimulate antitumor immunity in a murine model of pancreatic cancer.
Methods
Early endeavors have been focused on the downstream analysis of adaptive immune cell populations following TTFields treatment. A splenocyte stimulation assay was used to comparatively assess pancreatic tumor-bearing mice treated with TTFields and a panel of controls. To assess T-cell responses to a defined peptide antigen, splenocytes were first isolated from mice and red blood cells were lysed. Cells in complete-medium suspension were then stimulated ex-vivo with individual or pooled peptides that constitute minimal CD8 epitopes that are expressed from the Panc-02 pancreatic cancer cell line. Cytokine flow cytometry and enzyme-linked-immunospot (ELISpot) assays were utilized to quantify the production of interferon-gamma (IFN-γ) expressing T-cells.
Results
Preliminary data suggest that TTFields, employed as a monotherapy, resulted in detectable levels of activation of immune cells by tumor specific neoantigens. These experiments also revealed concomitant-treatment of TTFields with PancVax recruited 6.2-fold higher number of IFN-γ T-cells compared to TTFields alone.
Conclusion
There appeared to be synergistic antitumor effects when TTFields and the neoantigen vaccine PancVax were used to concomitantly treat a widely-used murine pancreatic cancer model. These preliminary findings support the hypothesis that TTFields can influence neoantigen recognition and/or T cell activation, and could thereby serve as a catalyst for future studies that can explore the addition of immunotherapy concomitantly treated with radiotherapy for optimal anti-tumor outcomes.