Abstract B107: Next generation of poxvirus-based immunotherapeutics

Oncolytic virus (OV) therapy has emerged as a promising approach for cancer treatment with the potential to be less toxic and more efficient than classic cancer therapies. Various types of OVs in clinical development, including Vaccinia virus (VACV)-derived OVs, have shown good safety profiles. We report here that a VACV can induce immunogenic cell death and generate a systemic immune response. Effects on tumor growth and survival was largely driven by CD8 T-cells, and immune cell infiltrate in the tumor could be reprogrammed toward a higher ratio of effector CD8 T-cells to regulatory CD4 T-cells. We demonstrate also the successful vectorization of a monoclonal anti-mPD-1 antibody in our VACV. The vectorized anti-mPD-1 antibody was able to block the binding of mPD-1 ligand to mPD-1 in vitro. Moreover, mAb was detected in tumor and in serum of C57BL/6 mice when the recombinant VACV was injected intratumorally (i.t.) in B16F10 and MCA 205 tumors. The concentration of circulating mAb detected after i.t. injection was up to 1,900-fold higher than the level obtained after a subcutaneous (s.c.) injection (i.e., without tumor), confirming the virus tropism for tumoral cells. Moreover, the overall tumoral accumulation of the mAb was higher and lasted longer after i.t. injection of the recombinant VACV than after i.t. administration of 10 µg of anti-mPD1. Interestingly, in the MCA 205 tumor model, the antitumoral activity of the VACV expressing mPD-1 is similar to the therapeutic efficacy of the combination of the unarmed VACV combined with a systemically administration of an anti-mPD-1 antibody and superior to that obtained with the unarmed VACV alone. These results pave the way for next generation of OV armed with immunomodulatory therapeutic molecules. Citation Format: Laetitia Fend. Next generation of poxvirus-based immunotherapeutics [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 B107.