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Chimeric antigen receptor T cells therapy in solid tumors

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Abstract

Chimeric antigen receptor T cells therapy (CAR-T therapy) is a class of ACT therapy. Chimeric antigen receptor (CAR) is an engineered synthetic receptor of CAR-T, which give T cells the ability to recognize tumor antigens in a human leukocyte antigen-independent (HLA-independent) manner and enables them to recognize more extensive target antigens than natural T cell surface receptor (TCR), resulting in tumor destruction. CAR-T is composed of an extracellular single-chain variable fragment (scFv) of antibody, which serves as the targeting moiety, hinge region, transmembrane spacer, and intracellular signaling domain(s). CAR-T has been developing in many generations, which differ according to costimulatory domains. CAR-T therapy has several limitations that reduce its wide availability in immunotherapy which we can summarize in antigen escape that shows either partial or complete loss of target antigen expression, so multiplexing CAR-T cells are promoted to enhance targeting of tumor profiles. In addition, the large diversity in the tumor microenvironment also plays a major role in limiting this kind of treatment. Therefore, engineered CAR-T cells can evoke immunostimulatory signals that rebalance the tumor microenvironment. Using CAR-T therapy in treating the solid tumor is mainly restricted by the difficulty of CAR-T cells infiltrating the tumor site, so local administration was developed to improve the quality of treatment. The most severe toxicity after CAR-T therapy is on-target/on-tumor toxicity, such as cytokine release syndrome (CRS). Another type of toxicity is on-target/off-tumor toxicity which originates from the binding of CAR-T cells to target antigen that has shared expression on normal cells leading to damage in healthy cells and organs. Toxicity management should become a focus of implementation to permit management beyond specialized centers.

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Authors and Affiliations

  1. Faculty of Medicine, Yarmouk University, Irbid, Jordan

    Fatimah Rababah, Taqwa Alabduh, AlHareth Awawdeh, Tareq Shatnawi, Maha AL-shdaifat, Elana Ibdah, Shatha Shatnawi, Yahia AbuZetun, Ahmed Mohamed Helaly & Doaa S. Ghorab

  2. Forensic and Toxicology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt

    Ahmed Mohamed Helaly

  3. Pathology Department, Mansoura University, Mansoura, Egypt

    Doaa S. Ghorab

Authors
  1. Fatimah Rababah
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  2. Taqwa Alabduh
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  3. AlHareth Awawdeh
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  4. Tareq Shatnawi
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  5. Maha AL-shdaifat
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  6. Elana Ibdah
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  7. Shatha Shatnawi
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  8. Yahia AbuZetun
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  9. Ahmed Mohamed Helaly
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  10. Doaa S. Ghorab
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Corresponding author

Correspondence to Ahmed Mohamed Helaly.

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The authors agreed that the corresponding author is responsible for the process of submission. The authors declared no submission to any other journal in the same time. The data mentioned in this review article are original.

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This review does not perform experimental work on animals or humans. The data were collected from the web base.

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Rababah, F., Alabduh, T., Awawdeh, A. et al. Chimeric antigen receptor T cells therapy in solid tumors. Clin Transl Oncol 25, 2279–2296 (2023). https://doi.org/10.1007/s12094-023-03122-8

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  • DOI: https://doi.org/10.1007/s12094-023-03122-8

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