Abstract 2497: Immune checkpoint inhibitors enhance benefits of modified vaccinia virus Ankara to improve survival in preclinical models of cancer

TG4010 is a Modified Vaccinia virus Ankara (MVA) expressing human interleukin 2 and the human mucin1 (MUC1) tumor associated antigen. TG4010 has demonstrated clinical benefit for advanced non small cell lung cancer patients in combination with standard of care chemotherapy in two phase 2 randomized and controlled clinical trials (NCT00415818 and NCT1383148). Immunotherapy based on the use of immune checkpoint blockers such as anti PD-1 and anti PD-L1 has also demonstrated efficacy in phase 2 trials. Hence, the combination of both approaches appears to be of great interest considering the high unmet medical need of this pathology. We developed experimental primary tumor and lung metastasis models to evaluate the rationale of combining both approaches at the preclinical level. Using two CT26 cell lines expressing different target antigens (β-galactosidase and MUC1) we evaluated the impact on overall survival of combined MVA-based and immune checkpoint-based immunotherapies. Synergistic increase in overall survival was observed in the therapeutic CT26-CL25 primary tumor and lung metastasis models upon treatment of mice with the combination of MVA-βgal and anti CTLA4 or anti PD-1 in comparison with either treatment alone. We provide evidence that TG4010 synergized with immune checkpoint inhibitors to increase overall survival in the therapeutic CT26-MUC1 tumor models in comparison with either treatment administrated independently. These observations were associated with an increase in the frequency and the quality of antigen-specific tumor infiltrating CD8+ T cells. These studies pave the way for the evaluation of combinatorial therapies including TG4010 and immune checkpoint blockers in the clinic. Citation Format: Karola Rittner, Christelle Remy-Ziller, Julie Hortelano, Isabelle Farine, Micael de Meyer, Virginie Nourtier, Murielle Gantzer, Christine Thioudellet, Philippe Slos, Xavier Preville. Immune checkpoint inhibitors enhance benefits of modified vaccinia virus Ankara to improve survival in preclinical models of cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2497. doi:10.1158/1538-7445.AM2015-2497