美国BioNTech公司Lakshmi Srinivasan和达纳·法伯癌症研究所Patrick A. Ott课题组合作取得一项新突破。他们的最新研究展示了个性化新抗原附加抗PD-1疗法在晚期黑色素瘤、非小细胞肺癌或膀胱癌患者中Ib期临床实验的结果。这一研究成果于2020年10月15日发表在国际学术期刊《细胞》上。
在本研究中，研究人员展示了首个开放性针对晚期黑素瘤、非小细胞肺癌或膀胱癌患者的个性化新抗原疫苗NEO-PV-01结合PD-1阻断疗法Ib期的临床试验结果。对82位患者的分析表明该方案是安全的并且未观察到与治疗相关的严重不良事件。
在所有患者接种疫苗后均能观察到针对新生抗原特异性的CD4+和CD8+ T细胞反应。疫苗诱导具有细胞毒性的T细胞，其能够转运至肿瘤并介导细胞杀伤。另外，在疫苗接种后诱导的新抗原表位不包括在疫苗中。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。
据介绍，新抗原来源于癌细胞中的突变，这是T细胞介导抗肿瘤免疫力的重要靶点。
附：英文原文
Title: 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
Author: Patrick A. Ott, Siwen Hu-Lieskovan, Bartosz Chmielowski, Ramaswamy Govindan, Aung Naing, Nina Bhardwaj, Kim Margolin, Mark M. Awad, Matthew D. Hellmann, Jessica J. Lin, Terence Friedlander, Meghan E. Bushway, Kristen N. Balogh, Tracey E. Sciuto, Victoria Kohler, Samantha J. Turnbull, Rana Besada, Riley R. Curran, Benjamin Trapp, Julian Scherer, Asaf Poran, Dewi Harjanto, Dominik Barthelme, Ying Sonia Ting, Jesse Z. Dong, Yvonne Ware, Yuting Huang, Zhengping Huang, Amy Wanamaker, Lisa D. Cleary, Melissa A. Moles, Kelledy Manson, Joel Greshock, Zakaria S. Khondker, Ed Fritsch, Michael S. Rooney, Mark DeMario, Richard B. Gaynor, Lakshmi Srinivasan
Issue&Volume: 2020/10/15
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).
DOI: 10.1016/j.cell.2020.08.053
Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31141-7