一项个体化新抗原治疗联合抗 PD-1 治疗晚期黑色素瘤、非小细胞肺癌或膀胱癌患者的 Ib 期临床试验。

A Phase Ib Trial of Personalized Neoantigen Therapy Plus Anti-PD-1 in Patients with Advanced Melanoma, Non-small Cell Lung Cancer, or Bladder Cancer.

机构信息

Dana Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.

Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

出版信息

Cell. 2020 Oct 15;183(2):347-362.e24. doi: 10.1016/j.cell.2020.08.053.

DOI:10.1016/j.cell.2020.08.053

PMID:33064988

Abstract

Neoantigens arise from mutations in cancer cells and are important targets of T cell-mediated anti-tumor immunity. Here, we report the first open-label, phase Ib clinical trial of a personalized neoantigen-based vaccine, NEO-PV-01, in combination with PD-1 blockade in patients with advanced melanoma, non-small cell lung cancer, or bladder cancer. This analysis of 82 patients demonstrated that the regimen was safe, with no treatment-related serious adverse events observed. De novo neoantigen-specific CD4 and CD8 T cell responses were observed post-vaccination in all of the patients. The vaccine-induced T cells had a cytotoxic phenotype and were capable of trafficking to the tumor and mediating cell killing. In addition, epitope spread to neoantigens not included in the vaccine was detected post-vaccination. These data support the safety and immunogenicity of this regimen in patients with advanced solid tumors (Clinicaltrials.gov: NCT02897765).

摘要

新抗原源于癌细胞的突变，是 T 细胞介导的抗肿瘤免疫的重要靶点。在这里，我们报告了一项个体化新抗原疫苗 NEO-PV-01 联合 PD-1 阻断剂治疗晚期黑色素瘤、非小细胞肺癌或膀胱癌的首次开放性、Ib 期临床试验。对 82 例患者的分析表明，该方案安全，未观察到与治疗相关的严重不良事件。所有患者在接种疫苗后均观察到新抗原特异性 CD4 和 CD8 T 细胞应答。疫苗诱导的 T 细胞具有细胞毒性表型，能够向肿瘤迁移并介导细胞杀伤。此外，接种疫苗后检测到针对疫苗中未包含的新抗原的表位扩展。这些数据支持该方案在晚期实体瘤患者中的安全性和免疫原性（Clinicaltrials.gov：NCT02897765）。