通过疫苗协同增强 CAR-T 细胞治疗

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通过疫苗协同增强 CAR-T 细胞治疗

英文原题：Boosting CAR-T cell therapy through vaccine synergy.

PubMed 2025/01/03（内容时间） Trends Pharmacol Sci Q1 · IF 24（JCR 2025）

技术：CAR-T 技术：mRNA 实体瘤地区：美国

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研究概要

嵌合抗原受体 (CAR)-T 细胞治疗已改变血液肿瘤的治疗格局。

中文摘要

嵌合抗原受体（CAR）T细胞疗法改变了血液系统癌症的治疗格局，但在实体瘤中取得同等成功仍具挑战。限制因素包括肿瘤特异性抗原（TSA）稀少、CAR-T细胞浸润不足以及免疫抑制性肿瘤微环境（TME）。疫苗策略正成为应对这些挑战的潜在方法，可增强CAR-T细胞扩增、持久性和抗肿瘤疗效。本文综述多种疫苗方式，包括mRNA、肽、病毒载体和树突状细胞（DC）疫苗，并讨论它们增强CAR-T细胞应答的作用。文章特别关注近期将mRNA疫苗与CAR-T疗法联合用于泌尿生殖系统癌症的临床进展。此外，本文还讨论如何优化疫苗剂量、给药时间安排和递送方式，以最大化其与CAR-T的协同作用，并改进这一联合策略的疗效和安全性。

展开英文摘要原文

Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment landscape for hematological cancers. However, achieving comparable success in solid tumors remains challenging. Factors contributing to these limitations include the scarcity of tumor-specific antigens (TSAs), insufficient CAR-T cell infiltration, and the immunosuppressive tumor microenvironment (TME). Vaccine-based strategies are emerging as potential approaches to address these challenges, enhancing CAR-T cell expansion, persistence, and antitumor efficacy. In this review, we explore diverse vaccine modalities, including mRNA, peptide, viral vector, and dendritic cell (DC)-based vaccines, and their roles in augmenting CAR-T cell responses. Special focus is given to recent clinical advancements combining mRNA-based vaccines with CAR-T therapy for the treatment of genitourinary cancers. In addition, we discuss crucial considerations for optimizing vaccine dosing, scheduling, and delivery to maximize CAR-T synergy, aiming to refine this combination strategy to improve treatment efficacy and safety.

论文信息

作者: Li YR、Lyu Z、Shen X、Fang Y、Yang L
第一作者单位: Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: charlie.li@ucla.edu.United States
通讯作者单位: Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Parker Institute for Cancer Immunotherapy, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: liliyang@ucla.edu.United States
文献类型: 综述 · 非美国政府资助研究
期刊: Trends in pharmacological sciences2025 Feb

原文标识: PubMed 39755457　·　DOI 10.1016/j.tips.2024.12.004

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