Checkpoint Inhibitor Combinations In A Human Mixed Leukocyte Reaction

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PAIn an effort to identify effective target combinations, molecules specific for several immuno-oncology targets were combined in vitro using a mixed leukocyte reaction (MLR) assay. Briefly, 20 different healthy human peripheral blood mononuclear cell donor pairs were tested for proliferation and cytokine release in the presence of each molecule alone and in combination. The collection of agents targeted CTLA-4, PD-1, PD-L1, and CD73. Examples of significant (pu003c0.05) synergy as well as antagonism and additivity were observed. In addition the phenotype and genotype of the MLR donor PBMCs were characterized. The results from this study are significant for at least two reasons: 1) In contrast to murine syngeneic models they represent aspects of multiple different human donor “immune responses” and 2) In contrast to purified T-cell assays they represent an assay system in which both the lymphoid and myeloid/innate immune compartments play a crucial role, and so better recapitulate a physiological T-cell response. Furthermore, these results provide information at the human population level, offering a glimpse of “responder” and “non-responder” population profiles. This information is impossible to obtain from the currently available collection of syngeneic mouse models.Citation Format: Erin Sult, Carl Hay, Qihui Huang, Stacy Fuhrmann, Robert Hollingsworth, Kris F. Sachsenmeier. Checkpoint inhibitor combinations in a human mixed leukocyte reaction. [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 272. doi:10.1158/1538-7445.AM2015-272