Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California.
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California
J Nucl Med. 2021 Feb;62(2):228-231. doi: 10.2967/jnumed.120.246041. Epub 2020 Jul 9.
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). C57BL/6-mice bearing syngeneic RM1-PGLS tumors were treated with Ac-PSMA617, an anti-PD-1 antibody, or both. Therapeutic efficacy was assessed by tumor volume measurements (CT), time to progression (TTP), and survival. PSMA RNT or anti-PD-1 alone tended to prolong TTP (isotype control, 25 d; anti-PD-1, 33.5 d [ = 0.0153]; RNT, 30 d [ = 0.1038]) and survival (control, 28 d; anti-PD-1, 37 d [ = 0.0098]; RNT, 32 d [ = 0.1018]). Combining PSMA RNT and anti-PD-1 significantly improved disease control compared with either monotherapy. TTP was extended to 47.5 d ( ≤ 0.0199 vs. monotherapies), and survival to 51.5 d ( ≤ 0.0251 vs. monotherapies). 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.
前列腺特异性膜抗原 (PSMA)-靶向放射性核素治疗 (RNT) 可能增加肿瘤的免疫原性。我们旨在通过在前列腺癌 (PC) 小鼠模型中将 RNT 与免疫疗法相结合来利用这种效应。 携带同源 RM1-PGLS 肿瘤的 C57BL/6 小鼠接受 Ac-PSMA617、抗 PD-1 抗体或两者的治疗。通过肿瘤体积测量 (CT)、进展时间 (TTP) 和生存来评估治疗效果。 PSMA RNT 或单独使用抗 PD-1 治疗均倾向于延长 TTP（同种型对照，25 天；抗 PD-1，33.5 天 [=0.0153]；RNT，30 天 [=0.1038]）和生存（对照，28 天；抗 PD-1，37 天 [=0.0098]；RNT，32 天 [=0.1018]）。与单独使用 RNT 或抗 PD-1 相比，联合使用 PSMA RNT 和抗 PD-1 可显著改善疾病控制。TTP 延长至 47.5 天（≤0.0199 与单药治疗相比），生存时间延长至 51.5 天（≤0.0251 与单药治疗相比）。 PSMA RNT 和 PD-1 阻断协同改善我们的 PC 模型中的治疗结果，支持对 PC 患者进行 RNT 和免疫疗法联合治疗的评估。
