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?:abstract
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Purpose: Prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy (RNT) may increase tumor immunogenicity. We aimed at exploiting this effect by combining RNT with immunotherapy in a mouse model of prostate cancer (PC). Experimental Design: C57BL/6-mice bearing syngeneic RM1-PGLS tumors were treated with 225Ac-PSMA617, an anti-PD-1 antibody, or both. Therapeutic efficacy was assessed by tumor volume measurements (computed tomography), time to progression (TTP) and survival. Results: PSMA-RNT or anti-PD-1 alone tended to prolong TTP (isotype-control 25d; anti-PD-1 33.5d, p=0.0153; RNT 30d, p=0.1038) and survival (control 28d; anti-PD-1 37d, p=0.0098; RNT 32d, p=0.1018). Combining PSMA-RNT and anti-PD-1 significantly improved disease control compared to either monotherapy. TTP was extended to 47.5d (p<0.0199 vs. monotherapies), and survival to 51.5d (p<0.0251 vs. monotherapies). Conclusion : PSMA-RNT and PD-1 blockade synergistically improve therapeutic outcomes in our PC model, supporting the evaluation of RNT/immunotherapy combinations for PC patients.
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