Efficacy And Immune Modulation Of The Tumor Microenvironment With The Combination Of The Parp Inhibitor Rucaparib And Cd122-Biased Agonist Nktr-214.

5582Background: NKTR-214 is a biased agonist of the IL2Rbg (CD122) pathway that activates and mobilizes CD8 T and NK cells into the tumor microenvironment. The PARP inhibitor rucaparib has demonstrated activity in BRCA mutant deficient tumors through synthetic lethality. We hypothesized that PARP inhibition in a BRCA syngeneic model would lead to immunogenic cell death and synergize with NKTR-214 through antigen priming and enhanced activation of newly infiltrated intratumoral T and NK cells. Methods: Mice (n = 10/group) were inoculated with the murine ovarian tumor cells (BR5FVB1) harboring genetic alterations (TP53-/-, BRCA1-/-, myc and Akt) frequently present in human ovarian carcinomas. Tumors were grown to 125 mm3prior to treatment with vehicle, rucaparib (150 mg/kg BID x 28 days), NKTR-214 (0.8 mg/kg q9d x 3), or the combination and tumor volumes were measured. Immune modulation was evaluated by IHC and gene expression. Results: Treatment with the combination resulted in 88.5% tumor growth inhibitio...