Abstract B141: Anti-tumor immune responses elicited by mesothelin virus-like particles vaccine effectively controls pancreatic cancer in animal models

Abstract

Pancreatic cancer is the 12th most common cancer, but is the 3rd leading cause of cancer death in America. This disparity is directly related to three factors: the difficulty in early detection of the disease, pancreatic cancer’s resistance to chemotherapy, and a tendency for the cancer to metastasize early and quickly. Here, we propose a novel immunotherapy to bypass pancreatic cancer’s resistance to standard chemotherapy. We have developed a virus-like particle (VLP) based on an HIV backbone Gag and pancreatic cancer-associated protein mesothelin (MSLN). Vaccination of C57BL/6 mice with MSLN VLP can efficiently activate the immune system and reduce and in some cases eliminate the host’s pancreatic cancer. Our results show that MSLN VLPs induce both humoral and cytotoxic specific response against MSLN in mouse pancreatic cancer models. Specifically, after vaccination with MSLN VLPs, significant increases in CD8+ MSLN specific T-cells and increases in serum anti-MSLN IgG were detected. Furthermore, we observed an increase in the serum of pro-inflammatory cytokine IFN-γ and B cell stimulator IL-5. Consistent with the increased IL-5, we observed a significant increase in tumor infiltrating B cells in the MSLN VLP immunized groups, but neither Gag VLP control nor unimmunized mice. Furthermore, while all tumor-bearing mice generated some antibodies towards MSLN, our MSLN VLP immunized mice had significantly higher serum titers of IgG1, IgG2B, and IgG3. Both Gag VLP and MSLN VLP immunized mice had a decreased tumor volume compared to control, but passive transfer of sera only from MSLN VLP immunized mice decreased tumor volume and increased survival of unimmunized tumor bearing mice, while Gag VLP immunized mice had much less effect. Overall, we have developed a promising vaccine for pancreatic cancer warranting additional studies with adjuvants and combination treatments with standard-of-care chemotherapy. Citation Format: Qizhi Cathy Yao, Ethen Poteet, Zhengdong Liang, Phoebe Lewis, Zhiyin Yu, Changyi Chen. Anti-tumor immune responses elicited by mesothelin virus-like particles vaccine effectively controls pancreatic cancer in animal models [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B141.