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Advancing CAR-based cell therapies for solid tumours: challenges, therapeutic strategies, and perspectives

Sarkar Sardar AzeezDepartment of Medical Laboratory Technology, Soran Technical College, Erbil Polytechnic University, Erbil, Kurdistan Region, 44008, IraqRaya Kh. YashooaDepartment of Biology, College of Education for Pure Sciences, University of Al-Hamdaniya, Mosul, 41002, IraqShukur Wasman SmailCollege of Pharmacy, Cihan University-Erbil, Erbil, Kurdistan Region, IraqAbbas SalihiCenter of Research and Strategic Studies, Lebanese French University, Kurdistan Region, Erbil, Kurdistan Region, 44002, IraqAzhin Saber AliDepartment of Medical Laboratory Technology, Shaqlawa Technical College, Erbil Polytechnic University, Erbil, Kurdistan Region, IraqSami MamandDepartment of Immunology, University of Toronto, Toronto, ON, CanadaChrister JansonDepartment of Medical Science, Respiratory Medicine, and Allergology, Uppsala University and University Hospital, Uppsala, Sweden. [email protected]

2025en

ABI

Annotatsiya

Chimeric antigen receptor-cell therapies have demonstrated remarkable success in haematological malignancies but face significant hurdles in solid tumours. The hostile tumour microenvironment, antigen heterogeneity, limited tumour infiltration, and CAR-cell exhaustion contribute to reduced efficacy. Additionally, toxicity, off-target effects, and manufacturing challenges limit widespread clinical adoption. Overcoming these barriers requires a multifaceted approach that enhances CAR-cell persistence, trafficking, and tumour-specific targeting. Recent advancements in alternative cellular therapies, such as CAR-natural killer cells, CAR-macrophages, gamma delta CAR-T cells, and CAR-natural killer T cells, provide promising avenues for improving efficacy. These strategies leverage distinct immune cell properties to enhance tumour recognition and persistence. Furthermore, combination therapies, including chemotherapy, radiotherapy, antibodies, small molecule inhibitors, cancer vaccines, oncolytic viruses, and multi-CAR cell combination therapy, offer synergistic potential by modulating the TME and improving CAR-cell functionality. This review explores the challenges of CAR-based cellular therapies in solid tumours and highlights emerging strategies to overcome therapeutic limitations. By integrating novel cellular platforms and combination approaches, we seek to provide insights into optimising CAR-cell therapies for durable responses in solid malignancies.

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DOI: 10.1186/s12943-025-02386-8

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