CAR-Based Cell and Gene Therapies: Global Clinical Landscape and Emerging Therapeutic Strategies from ClinicalTrials.gov

Abstract

Chimeric Antigen Receptor (CAR)-based cell and gene therapies have become transformative treatments, offering targeted and durable responses, especially in hematologic malignancies. This review analyzes 1,744 CAR clinical trials registered on ClinicalTrials.gov as of 2024, focusing on platform types, indications, target antigens, therapeutic strategies, and late-phase development. CAR-T therapies predominate, followed by CAR-NK, CAR-NKT, CAR-M and CAR-DC platforms. Approximately 92% of trials target tumors, with hematologic malignancies accounting for 65% of indications; CD19 and BCMA are primary targets in Phase 3 studies. Solid tumor applications are expanding steadily, driven by unmet clinical needs and advances in CAR engineering. Although monospecific CARs dominate, dual, bispecific, and universal designs are gaining traction to overcome antigen heterogeneity and tumor escape. Combination therapies, such as CAR-T with chemotherapy or monoclonal antibodies, are increasingly used to improve efficacy. CAR-NK therapies, while in early development, show promise due to favorable safety profiles and off-the-shelf allogeneic potential. The United States and China lead global development, supported by robust research ecosystems and industrial investment. Overall, CAR-based therapeutics are evolving from hematologic specialization toward broader clinical application, addressing challenges and guiding future strategies.