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

Authors :
Karama Makni Maalej
Maysaloun Merhi
Varghese P. Inchakalody
Sarra Mestiri
Majid Alam
Cristina Maccalli
Honar Cherif
Shahab Uddin
Martin Steinhoff
Francesco M. Marincola
Said Dermime
Source :
Molecular Cancer, Vol 22, Iss 1, Pp 1-54 (2023)
Publication Year :
2023
Publisher :
BMC, 2023.

Abstract

Abstract 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.

Details

Language :
English
ISSN :
14764598
Volume :
22
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Molecular Cancer
Publication Type :
Academic Journal
Accession number :
edsdoj.7971c1c1f7b74ee4a963643e95c66a43
Document Type :
article
Full Text :
https://doi.org/10.1186/s12943-023-01723-z