Combination Neoantigen-Based Dendritic Cell Vaccination and Adoptive T-Cell Transfer Induces Antitumor Responses Against Recurrence of Hepatocellular Carcinoma.
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| Abstract |
A high rate of recurrence after curative therapy is a major challenge for the management of hepatocellular carcinoma (HCC). Currently, no effective adjuvant therapy is available to prevent HCC recurrence. We designed a personalized neoantigen-loaded dendritic cell vaccine and neoantigen-activated T-cell therapy, and used it as adjuvant therapy to treat 10 patients with HCC who had undergone curative resection or radiofrequency ablation in the first stage of a phase II trial (NCT03067493). The primary outcomes were safety and neoantigen-specific immune response. Disease-free survival (DFS) was also evaluated. The immunotherapy was successfully administered to all the patients without unexpected delay and demonstrated a reasonable safety profile with no grade ≥3 treatment-related side effects reported. Seventy percent of patients generated de novo circulating multiclonal neoantigen-specific T-cell responses. Induced neoantigen-specific immunity was maintained over time, and epitope spreading was observed. Patients who generated immune responses to treatment exhibited prolonged DFS compared with nonresponders (P = 0.012), with 71.4% experiencing no relapse for 2 years after curative treatment. High expression of an immune stimulatory signature, enhanced immune-cell infiltration (i.e., CD8+ T cells), and upregulated expression of T-cell inflammatory gene profiles were found in the primary tumors of the responders. In addition, neoantigen depletion (immunoediting) was present in the recurrent tumors compared with the primary tumors (7/9 vs. 1/17, P = 0.014), suggesting that immune evasion occurred under the pressure of immunotherapy. Our study indicates that neoantigen-based combination immunotherapy is feasible, safe, and has the potential to reduce HCC recurrence after curative treatment.
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| Authors | Sui Peng, Shuling Chen, Wei Hu, Jie Mei, Xuezhen Zeng, Tianhong Su, Wei Wang, Zebin Chen, Han Xiao, Qian Zhou, Bin Li, Yubin Xie, Huanjing Hu, Minghui He, Yanyan Han, Longqing Tang, Yifan Ma, Xiaoshuang Li, Xiangjun Zhou, Zihao Dai, Zelong Liu, Jiehui Tan, Lixia Xu, Shaoqiang Li, Shunli Shen, Dongming Li, Jiaming Lai, Baogang Peng, Zhenwei Peng, Ming Kuang |
| Journal | Cancer immunology research (Cancer Immunol Res) Vol. 10 Issue 6 Pg. 728-744 (06 03 2022) ISSN: 2326-6074 [Electronic] United States |
| PMID | 35476700 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | ©2022 American Association for Cancer Research. |
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