Journal Article

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

Janson, Christer, Yashooa, Raya Kh, Mamand, Sami, Azeez, Sarkar Sardar, Salihi, Abbas, Ali, Azhin Saber, Smail, Shukur Wasman

2025

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Angiogenesis / Animals / Antigen presentation / Antigens / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer Research / Cancer therapies / Cancer vaccines / CAR-Macrophages / CAR-NK cells / CAR-T cells / Care and treatment / Cell therapy / Cells / Challenges / Chemotherapy / Chimeric antigen receptors / Clinical trials / Combination therapy / Combined Modality Therapy / Cytokines / Cytotoxicity / Development and progression / FDA approval / Health aspects / Hematology / Humans / Hypoxia / Immunotherapy / Immunotherapy, Adoptive - methods / Killer cells / Lymphocytes / Lymphocytes T / Lymphoma / Macrophages / Malignancy / Metabolism / Metastases / Natural killer cells / Neoplasms - etiology / Neoplasms - immunology / Neoplasms - therapy / Oncology / Oncolysis / Optimisation Strategies / Radiation therapy / Radiotherapy / Receptors, Chimeric Antigen - genetics / Receptors, Chimeric Antigen - immunology / Receptors, Chimeric Antigen - metabolism / Response rates / Review / Solid tumors / T cells / Toxicity / Tumor microenvironment / Tumor Microenvironment - immunology / Tumors