Neoantigen vaccination induces clinical and immunologic responses in non-small cell lung cancer patients harboring EGFR mutations

作者：Fenge Li, Ligang Deng, Kyle R. Jackson, Amjad H. Talukder, Arjun Katailiha, Sherille D. Bradley, Qingwei Zou, Caixia Chen, Chong Huo, Yulun Chiu, Matthew Stair, Weihong Feng, A. Bagaev, Nikita Kotlov, Viktor Svekolkin, Ravshan Ataullakhanov, Natalia Miheecheva, Felix Frenkel, Yaling Wang, Minying Zhang, David H. Hawke, Ling Han, Shuo Zhou, Yan Zhang, Zhenglu Wang, William K. Decker, Heather M. Sonnemann, Jason Roszik, Marie-Andrée Forget, Michael A. Davies, Chantale Bernatchez, Cassian Yee, Roland L. Bassett, Patrick Hwu, Xueming Du, Gregory Lizée · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2021 · DOI：10.1136/jitc-2021-002531 · 被引用次数：70 · 研究领域：Cancer Immunotherapy and Biomarkers、Immunotherapy and Immune Responses、vaccines and immunoinformatics approaches

BACKGROUND: Neoantigen (NeoAg) peptides displayed at the tumor cell surface by human leukocyte antigen molecules show exquisite tumor specificity and can elicit T cell mediated tumor rejection. However, few NeoAgs are predicted to be shared between patients, and none to date have demonstrated therapeutic value in the context of vaccination. METHODS: We report here a phase I trial of personalized NeoAg peptide vaccination (PPV) of 24 stage III/IV non-small cell lung cancer (NSCLC) patients who had previously progressed following multiple conventional therapies, including surgery, radiation, chemotherapy, and tyrosine kinase inhibitors (TKIs). Primary endpoints of the trial evaluated feasibility, tolerability, and safety of the personalized vaccination approach, and secondary trial endpoints assessed tumor-specific immune reactivity and clinical responses. Of the 16 patients with epidermal growth factor receptor (EGFR) mutations, nine continued TKI therapy concurrent with PPV and seven patients received PPV alone. RESULTS: Out of 29 patients enrolled in the trial, 24 were immunized with personalized NeoAg peptides. Aside from transient rash, fatigue and/or fever observed in three patients, no other treatment-related adverse events were observed. Median progression-free survival and overall survival of the 24 vaccinated patients were 6.0 and 8.9 months, respectively. Within 3-4 months following initiation of PPV, seven RECIST-based objective clinical responses including one comp...