Boosting CAR-T cell therapy through vaccine synergy

Yan-Ruide Li; Zibai Lyu; Xinyuan Shen; Ying Fang; Lili Yang

doi:10.1016/j.tips.2024.12.004

Boosting CAR-T cell therapy through vaccine synergy

Trends Pharmacol Sci. 2025 Jan 3:S0165-6147(24)00270-0. doi: 10.1016/j.tips.2024.12.004. Online ahead of print.

Authors

Yan-Ruide Li¹, Zibai Lyu², Xinyuan Shen², Ying Fang², Lili Yang³

Affiliations

¹ 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: [email protected].
² 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.
³ 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: [email protected].

PMID: 39755457
DOI: 10.1016/j.tips.2024.12.004

Abstract

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.

Keywords: CAR-engineered T (CAR-T) cell therapy; chimeric antigen receptor (CAR); dendritic cell-based vaccines; immunotherapy; mRNA vaccines; peptide vaccines; solid tumor therapy; tumor microenvironment; vaccine synergy; viral vector vaccines.

Publication types

Review