Immune-Checkpoint Blockade Enhances 225Ac-PSMA617 Efficacy in a Mouse Model of Prostate Cancer
Immune-Checkpoint Blockade Enhances 225Ac-PSMA617 Efficacy in a Mouse Model of Prostate Cancer
复制标题
DOI：
10.2967/jnumed.120.246041
复制
发表时间：
2021-02-01
影响因子：
9.3
通讯作者：
Luckerath, Katharina
中科院分区：
文献类型：
--
作者：
Czernin, Johannes;Current, Kyle;Luckerath, Katharina
前列腺特异性膜抗原（PSMA）靶向放射性核素治疗（RNT）可提高肿瘤的免疫原性。我们的目的是通过在前列腺癌（PC）小鼠模型中结合RNT和免疫治疗来利用这种效应。方法：用（225）AcPSMA617、抗pd -1抗体或两者同时治疗携带同源RM1-PGLS肿瘤的C57BL/6小鼠。通过肿瘤体积测量（CT）、进展时间（TTP）和生存率来评估治疗效果。结果：PSMA RNT或抗pd -1单用均可延长TTP（同型对照，25 d；抗pd -1, 33.5 d [P = 0.0153]； RNT, 30 d [P = 0.1038]）和生存期（对照组，28 d；抗pd -1, 37 d [P = 0.0098]； RNT, 32 d [P = 0.1018]）。与单药治疗相比，PSMA RNT和抗pd -1联合治疗显著改善了疾病控制。TTP延长至47.5 d (P
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 (225)AcPSMA617, 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