CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances

Molecular Cancer

Review

Honar Cherif¹  Francesco M. Marincola²  Cristina Maccalli³  Sarra Mestiri⁴  Varghese P. Inchakalody⁴  Karama Makni Maalej⁴  Maysaloun Merhi⁴  Said Dermime⁵  Shahab Uddin⁶  Majid Alam⁷  Martin Steinhoff⁸ 

[1] Department of Hematology, National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar;Global Head of Research, Kite Pharma, Santa Monica, California, USA;Laboratory of Immune and Biological Therapy, Research Department, Sidra Medicine, Doha, Qatar;Translational Cancer Research Facility, National Center for Cancer Care and Research, Translational Research Institute, Hamad Medical Corporation, P.O. Box: 3050, Doha, Qatar;Translational Cancer Research Facility, National Center for Cancer Care and Research, Translational Research Institute, Hamad Medical Corporation, P.O. Box: 3050, Doha, Qatar;College of Health and Life Sciences (CHLS), Hamad Bin Khalifa University, Doha, Qatar;Translational Research Institute, Academic Health System, Dermatology Institute, Hamad Medical Corporation, Doha, Qatar;Translational Research Institute, Academic Health System, Dermatology Institute, Hamad Medical Corporation, Doha, Qatar;Department of Dermatology and Venereology, Hamad Medical Corporation, Doha, Qatar;Translational Research Institute, Academic Health System, Dermatology Institute, Hamad Medical Corporation, Doha, Qatar;Department of Dermatology and Venereology, Hamad Medical Corporation, Doha, Qatar;Department of Dermatology, Weill Cornell Medicine-Qatar, Doha, Qatar;College of Medicine, Qatar University, Doha, Qatar;Department of Dermatology, Weill Cornell Medicine, New York, USA;

关键词: CAR-T;    CAR-NK;    CAR-M;    Cellular immunotherapy;    Solid tumors;    Combined therapies;   

DOI  :  10.1186/s12943-023-01723-z

 received in 2022-12-14, accepted in 2023-01-16,  发布年份 2023

来源: Springer

【 摘 要 】

In the last decade, Chimeric Antigen Receptor (CAR)-T cell therapy has emerged as a promising immunotherapeutic approach to fight cancers. This approach consists of genetically engineered immune cells expressing a surface receptor, called CAR, that specifically targets antigens expressed on the surface of tumor cells. In hematological malignancies like leukemias, myeloma, and non-Hodgkin B-cell lymphomas, adoptive CAR-T cell therapy has shown efficacy in treating chemotherapy refractory patients. However, the value of this therapy remains inconclusive in the context of solid tumors and is restrained by several obstacles including limited tumor trafficking and infiltration, the presence of an immunosuppressive tumor microenvironment, as well as adverse events associated with such therapy. Recently, CAR-Natural Killer (CAR-NK) and CAR-macrophages (CAR-M) were introduced as a complement/alternative to CAR-T cell therapy for solid tumors. CAR-NK cells could be a favorable substitute for CAR-T cells since they do not require HLA compatibility and have limited toxicity. Additionally, CAR-NK cells might be generated in large scale from several sources which would suggest them as promising off-the-shelf product. CAR-M immunotherapy with its capabilities of phagocytosis, tumor-antigen presentation, and broad tumor infiltration, is currently being investigated. Here, we discuss the emerging role of CAR-T, CAR-NK, and CAR-M cells in solid tumors. We also highlight the advantages and drawbacks of CAR-NK and CAR-M cells compared to CAR-T cells. Finally, we suggest prospective solutions such as potential combination therapies to enhance the efficacy of CAR-cells immunotherapy.

【 授权许可】

CC BY   
© The Author(s) 2023

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