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). Methods: 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 (CT), time to progression (TTP), and survival. Results: PSMA RNT or anti-PD-1 alone tended to prolong TTP (isotype control, 25 d; anti-PD-1, 33.5 d [P = 0.0153]; RNT, 30 d [P = 0.1038]) and survival (control, 28 d; anti-PD-1, 37 d [P = 0.0098]; RNT, 32 d [P = 0.1018]). Combining PSMA RNT and anti-PD-1 significantly improved disease control compared with either monotherapy. TTP was extended to 47.5 d (P ≤ 0.0199 vs. monotherapies), and survival to 51.5 d (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 and immunotherapy combinations for PC patients.
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). Methods: 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 (CT), time to progression (TTP), and survival. Results:PSMA RNT or anti-PD-1 alone tended to prolong TTP (isotype control, 25 d; anti-PD-1, 33.5 d [P = 0.0153]; RNT, 30 d [P = 0.1038]) and survival (control, 28 d; anti-PD-1, 37 d [P = 0.0098]; RNT, 32 d [P = 0.1018]). Combining PSMA RNT and anti-PD-1 significantly improved disease control compared with either monotherapy. TTP was extended to 47.5 d (P ≤ 0.0199 vs. monotherapies), and survival to 51.5 d (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 and immunotherapy combinations for PC patients.
Authors: Andreea D Stuparu; Joseph R Capri; Catherine A L Meyer; Thuc M Le; Susan L Evans-Axelsson; Kyle Current; Mark Lennox; Christine E Mona; Wolfgang P Fendler; Jeremie Calais; Matthias Eiber; Magnus Dahlbom; Johannes Czernin; Caius G Radu; Katharina Lückerath; Roger Slavik Journal: J Nucl Med Date: 2020-12-04 Impact factor: 10.057
Authors: Justin C Jagodinsky; Won Jong Jin; Amber M Bates; Reinier Hernandez; Joseph J Grudzinski; Ian R Marsh; Ishan Chakravarty; Ian S Arthur; Luke M Zangl; Ryan J Brown; Erin J Nystuen; Sarah E Emma; Caroline Kerr; Peter M Carlson; Raghava N Sriramaneni; Jonathan W Engle; Eduardo Aluicio-Sarduy; Todd E Barnhart; Trang Le; KyungMann Kim; Bryan P Bednarz; Jamey P Weichert; Ravi B Patel; Zachary S Morris Journal: Theranostics Date: 2021-04-15 Impact factor: 11.600
Authors: Mike M Sathekge; Frank Bruchertseifer; Mariza Vorster; Alfred Morgenstern; Ismaheel O Lawal Journal: Eur J Nucl Med Mol Imaging Date: 2021-06-26 Impact factor: 9.236