Abstract 3765: An anti-CD137 antibody can show greater efficacy in syngeneic mouse tumor models when combined with other immuno-oncology (IO) therapies

Abstract

Abstract CD137 is a costimulatory molecule associated with tumour infiltrating lymphocytes and cytotoxic T lymphocytes in particular. Murine anti-CD137 monoclonal antibodies (mAbs) have shown potent anti-tumour effects in syngeneic tumour models, which can be further enhanced by combination with checkpoint inhibitor (CPI) mAbs to PD-1, or CTLA-4 and OX40. Two anti-CD137 monoclonal antibodies (mAbs), Urelumab and Utomilumab, are in development for both haematological and solid cancers, and studies include combinations with other IO therapies such as anti-PD-1, anti-PD-L1 and anti-OX40 mabs. We studied the impact of combining anti-CD137 with CPIs anti-PD-L1, anti-CTLA4, and IO agonist GITRL fusion protein (GITRL-FP) and anti-OX40 on pharmacodynamic responses, tumour growth and survival in mouse syngeneic models. In a responsive model, CT26, combining anti-CD137 with anti-PD-L1 had a greater impact on tumour growth inhibition, which correlated with an enhanced proliferation of CD8 T cells, as determined Ki67 expression using flow cytometry. In MC-38, a model that is less sensitive to both monotherapies, the combination was synergistic and resulted in enhanced tumour growth inhibition. Next, we compared the anti-CTLA4, anti-OX40 and GITRL-FP as monotherapies and in combination with anti-CD137 in the CT26 model. As before, anti-CD137 alone induced CD8 T cell proliferation, whereas anti-OX40 and GITRL-FP stimulated expansion of CD8 and CD4 T cells. Interestingly, in all combinations anti-CD137 appeared to enhance both CD8 and CD4 T cell proliferation. Anti-CTLA4 and GITR-FP had a greater impact on tumour growth inhibition when combined with anti-CD137. In summary, in vivo models indicate that anti-CD137 mAbs are a promising therapy in cancer, but the most benefit may be obtained in combination with other IO therapies. Citation Format: Matthew J. Robinson, Ines Osma-Garcia, Jane Coates-Ulrichisen, Amanda Watkins, Suzanne Mosely, Chrisopher Lloyd, Geoff Williams, Michelle Morrow, Simon Dovedi, Ronald Herbst, Robert Wilkinson. An anti-CD137 antibody can show greater efficacy in syngeneic mouse tumor models when combined with other immuno-oncology (IO) therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3765.