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Purpose of Review <p>Chimeric antigen receptors (CARs) are manually manufactured fusion proteins designed to guide T lymphocytes against certain tumor-associated antigens. CAR-T cell therapy has considerably progressed the treatment of various cancer types, particularly hematological malignancies. This review discusses recent advancement in CAR-T cells, with an emphasis on dual-target and combination strategies across diverse tumor models.</p> Recent Findings <p>The effectiveness of CAR-T cell therapy, particularly in solid tumors remains limited due to challenges such as antigen escape and relapse, antigen heterogeneity, off-tumor toxicity, an immunosuppressive tumor microenvironment, and impaired T cell trafficking. To address these obstacles, recent advancements have focused on combinatorial approaches—including dual-targeting CARs that simultaneously recognize two antigens, co-administration with immune checkpoint inhibitors or small molecules, and cytokine modulation—to improve therapeutic efficacy and safety across a broader spectrum of cancers.</p> Summary <p>This review explores the evolving landscape of CAR-T cell therapies, emphasizing cutting-edge advances in CAR design—particularly those targeting selective antigen pairings. It also summarizes combinatorial strategies that show promise in overcoming current challenges and enhancing therapeutic efficacy. Finally, we discuss the future directions in CAR-T cell therapies, underscoring the importance of continued innovation to address the challenges and optimize the efficacy of this emerging immunotherapeutic modality.</p>

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Recent Advances in CAR-T Cell Therapy: from Dual Targeting To Emerging Innovations

  • 期刊论文

  • 发表日期：

    2025年8月20日

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  • Haris Saeed,
  • Tevah Nesvisky,
  • Shadab Kazmi,
  • Shamshul Huda,
  • Sehbanul Islam

摘要

Purpose of Review

Chimeric antigen receptors (CARs) are manually manufactured fusion proteins designed to guide T lymphocytes against certain tumor-associated antigens. CAR-T cell therapy has considerably progressed the treatment of various cancer types, particularly hematological malignancies. This review discusses recent advancement in CAR-T cells, with an emphasis on dual-target and combination strategies across diverse tumor models.

Recent Findings

The effectiveness of CAR-T cell therapy, particularly in solid tumors remains limited due to challenges such as antigen escape and relapse, antigen heterogeneity, off-tumor toxicity, an immunosuppressive tumor microenvironment, and impaired T cell trafficking. To address these obstacles, recent advancements have focused on combinatorial approaches—including dual-targeting CARs that simultaneously recognize two antigens, co-administration with immune checkpoint inhibitors or small molecules, and cytokine modulation—to improve therapeutic efficacy and safety across a broader spectrum of cancers.

Summary

This review explores the evolving landscape of CAR-T cell therapies, emphasizing cutting-edge advances in CAR design—particularly those targeting selective antigen pairings. It also summarizes combinatorial strategies that show promise in overcoming current challenges and enhancing therapeutic efficacy. Finally, we discuss the future directions in CAR-T cell therapies, underscoring the importance of continued innovation to address the challenges and optimize the efficacy of this emerging immunotherapeutic modality.