CAR-T therapy in solid tumors

Bing Du; Juliang Qin; Boxu Lin; Jiqin Zhang; Dali Li; Mingyao Liu

doi:10.1016/j.ccell.2025.03.019

CAR-T therapy in solid tumors

Cancer Cell. 2025 Apr 14;43(4):665-679. doi: 10.1016/j.ccell.2025.03.019.

Authors

Bing Du¹, Juliang Qin², Boxu Lin², Jiqin Zhang², Dali Li², Mingyao Liu³

Affiliations

¹ Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China. Electronic address: bdu@bio.ecnu.edu.cn.
² Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
³ Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China. Electronic address: myliu@bio.ecnu.edu.cn.

PMID: 40233718
DOI: 10.1016/j.ccell.2025.03.019

Abstract

While chimeric antigen receptor (CAR) T cell therapy has shown great success in hematologic malignancies, the effectiveness in solid tumors has been limited by several factors, including antigenic heterogeneity and the immunosuppressive nature of the tumor microenvironment (TME). In this review, we discuss the advancements made in clinical studies and challenges faced by CAR-T therapy for solid tumors. To enhance CAR-T cell efficacy in solid tumors, we explore strategies such as enhancing T cell persistence and cytotoxicity, targeting multiple antigens, and utilizing innovative allogeneic CAR-T cell manufacturing. Additionally, we highlight the potential benefits of combining CAR-T therapies with immune checkpoint inhibitors and other treatment modalities to overcome TME limitations. We remain optimistic about the future of CAR-T cell therapy in solid tumors, emphasizing the need for continued research to refine therapeutic approaches and address the clinical needs of patients with cancer.

Keywords: CAR-T; gene editing; solid tumor; synthetic biology; tumor microenvironment.

Publication types

Review

MeSH terms

Animals
Humans
Immunotherapy, Adoptive* / methods
Neoplasms* / immunology
Neoplasms* / therapy
Receptors, Antigen, T-Cell / immunology
Receptors, Chimeric Antigen* / immunology
T-Lymphocytes* / immunology
Tumor Microenvironment / immunology

Substances

Receptors, Chimeric Antigen
Receptors, Antigen, T-Cell