Abstract 4569: DNA vaccine targeting BARF1 induces potent antitumor immunity against Epstein-Barr virus-associated carcinomas

Abstract

Abstract Epstein-Barr Virus (EBV) is an oncogenic pathogen, with which more than 90% of world population has been infected. It is associated with several types of cancer, and no EBV-specific therapies are available for these diseases. Recent studies targeting EBV latent proteins have shown limited efficacy, for their moderate immunogenicity. Therefore, the development of effective anti-EBV immunotherapies is in need. In this study, we screened a group of EBV proteins and selected BARF1 as a vaccine candidate, for its strong immunogenicity and high expression in EBV positive nasopharyngeal and gastric carcinomas. The BARF1 vaccine was developed through a synthetic DNA approach and delivered in vivo by electroporation. The vaccine induced potent BARF1-specific antibody and polyfunctional effector T cell responses in both C57BL/6 and BALB/c mice. We next established two carcinoma models by generating BARF1-expressing CT26 and MC38 cell lines. In the therapeutic model where mice were challenged with cancer cells and then treated, BARF1 vaccine was able to suppress cancer progression alone and showed synergy when combined with anti-PD1 antibody. In the minimal residual disease model where mice were immunized and then challenged with cancer cells, one dose of BARF1 vaccine was able to generate 100% complete response in treated animals. CD8 T cell was shown to be necessary for this protection. Finally, using the in vivo imaging system, we found that the BARF1 vaccine-induced immune responses cleared tumor in 60% of subjects as soon as 48 hours post tumor challenge. Tumors were cleared in all animals by day 10. In summary, BARF1 DNA vaccine provides a novel tool of immunotherapy that is highly specific to EBV positive malignancies and combining it with checkpoint inhibitors might open up new avenues for precision and combination immunotherapy against EBV-associated cancer. In the future, we will also target other viral-specific cancer antigens with our DNA vaccine platform, exploiting its capability to induce potent cytotoxic T lymphocyte response. Citation Format: Xizhou Zhu. DNA vaccine targeting BARF1 induces potent antitumor immunity against Epstein-Barr virus-associated carcinomas [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4569.