免疫检查点阻断增强了前列腺癌小鼠模型中 Ac-PSMA617 的疗效。
Immune-Checkpoint Blockade Enhances Ac-PSMA617 Efficacy in a Mouse Model of Prostate Cancer.
机构信息
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
出版信息
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。
Zotero 插件