| Literature DB >> 33064988 |
Patrick A Ott1, Siwen Hu-Lieskovan2, Bartosz Chmielowski2, Ramaswamy Govindan3, Aung Naing4, Nina Bhardwaj5, Kim Margolin6, Mark M Awad7, Matthew D Hellmann8, Jessica J Lin9, Terence Friedlander10, Meghan E Bushway11, Kristen N Balogh11, Tracey E Sciuto11, Victoria Kohler11, Samantha J Turnbull11, Rana Besada11, Riley R Curran11, Benjamin Trapp11, Julian Scherer11, Asaf Poran11, Dewi Harjanto11, Dominik Barthelme11, Ying Sonia Ting11, Jesse Z Dong11, Yvonne Ware11, Yuting Huang11, Zhengping Huang11, Amy Wanamaker11, Lisa D Cleary11, Melissa A Moles11, Kelledy Manson11, Joel Greshock11, Zakaria S Khondker11, Ed Fritsch11, Michael S Rooney11, Mark DeMario11, Richard B Gaynor11, Lakshmi Srinivasan12.
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).Entities:
Keywords: NEO-PV-01; T cell; anti-PD-1; cancer vaccine; checkpoint inhibitor; epitope spread; immunotherapy; metastatic cancer; neoantigen; personalized vaccine
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Year: 2020 PMID： 33064988 DOI： 10.1016/j.cell.2020.08.053
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582