Next-Generation CAR-T and TCR-T Cell Therapies for Solid Tumors: Innovations, Challenges, and Global Development Trends

Abstract

Chimeric antigen receptor (CAR)-T and T-cell receptor (TCR)-engineered T-cell (TCR-T) therapies have revolutionized the treatment of hematological malignancies; however, their application to solid tumors remains a formidable challenge. The immunosuppressive tumor microenvironment, antigen heterogeneity, and manufacturing complexity limit the clinical efficacy and scalability of these treatment modalities. This review provides a comprehensive analysis of the current clinical development strategies for CAR-T and TCR-T cell therapies for solid tumors. Herein, we discuss recent breakthroughs and highlight the potential of TCR-T cell therapy. Furthermore, innovative approaches for enhancing CAR-T cell function in solid tumors (e.g., in vivo engineering; induced pluripotent stem cell-derived allogeneic CAR-T cells; armored CAR constructs; dual-antigen targeting; and combination regimens with checkpoint inhibitors, chemotherapy, radiotherapy, and oncolytic viruses) are explored. We also present trends in global patent activity, revealing a marked acceleration in CAR-T- and TCR-T-related innovations, with the United States and China leading with respect to application volumes. This field is increasingly characterized by multidisciplinary collaborations between academia and industry, driving the development of next-generation platforms, including messenger RNA-based and off-the-shelf cell therapies. Although no CAR-T product has been approved for solid tumors, these findings underscore the accelerating momentum and translational promise of adoptive cell therapies. Addressing the unique biological and logistical challenges of solid tumors is essential for realizing the full potential of these transformative immunotherapies.

Keywords: CAR-T cell therapy; TCR-T cell therapy; adoptive cell therapy; intellectual property; patent landscape; solid tumors.

Figure 1

Schematic illustration of CAR-T and TCR-T cell therapies. This figure presents a conceptual diagram of CAR-T cell therapy and TCR-T cell therapy. Abbreviations: CAR, chimeric antigen receptor; CAR-T, chimeric antigen receptor T-cell; CTL, Cytotoxic T Lymphocyte; HLA, human leukocyte antigen; TCR, T-cell receptor; TCR-T, T-cell receptor-engineered T-cell.

Figure 2

(A). Priority filing countries for CAR-T and TCR-T cell therapies. Countries where patent priority rights are claimed for CAR-T and TCR-T cell therapies are based on searches using a global patent database (Derwent Innovation-DWPI) and a pharmaceutical patent database (CCI-Patents). The vertical axis indicates the number of patent applications (≒primary development site), and the horizontal axis represents the year. The data from 2021–2023 are provisional and presented as reference values. (B). Most frequently designated countries for patent filings and the number of patents in CAR-T and TCR-T cell therapies. Countries most frequently designated as filing destinations for CAR-T and TCR-T cell-related patents are identified through the Derwent Innovation-DWPI and CCI-Patents databases. The vertical axis indicates the number of patent applications (≒market), and the horizontal axis represents the year. The data from 2021–2023 are provisional and presented as reference values.