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Review
. 2023 Dec 5:13:1288383.
doi: 10.3389/fonc.2023.1288383. eCollection 2023.

CAR-T treatment for cancer: prospects and challenges

Ran Chen #  1 , Lei Chen #  2 , Chaoqun Wang  1 , Hua Zhu  1 , Lijuan Gu  3 , Yuntao Li  1 , Xiaoxing Xiong  1 , Gang Chen  1 , Zhihong Jian  1
Affiliations
Review

CAR-T treatment for cancer: prospects and challenges

Ran Chen et al. Front Oncol. .

Abstract

Chimeric antigen receptor (CAR-T) cell therapy has been widely used in hematological malignancies and has achieved remarkable results, but its long-term efficacy in solid tumors is greatly limited by factors such as the tumor microenvironment (TME). In this paper, we discuss the latest research and future views on CAR-T cell cancer immunotherapy, compare the different characteristics of traditional immunotherapy and CAR-T cell therapy, introduce the latest progress in CAR-T cell immunotherapy, and analyze the obstacles that hinder the efficacy of CAR-T cell therapy, including immunosuppressive factors, metabolic energy deficiency, and physical barriers. We then further discuss the latest therapeutic strategies to overcome these barriers, as well as management decisions regarding the possible safety issues of CAR-T cell therapy, to facilitate solutions to the limited use of CAR-T immunotherapy.

Keywords: CAR-T; cancer immunotherapy; immune checkpoint; immunosuppressive environment; tumor microenvironment.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
CAR-T biological structure.
Figure 2
Figure 2
Increased expression of programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) reduces T-cell receptor (TCR) signaling sensitivity and leads to its dysfunction. Immunosuppressive cytokines and immunosuppressive cells (myeloid-derived suppressor MDSCs, tumor-associated macrophages (TAMs), and Treg cells hinder the effective antitumor function of CART cells. M1 phenotypic TAMs can phagocytose and kill tumor cells. M2 phenotypic TAMs put TME into an immunosuppressive state, which promotes tumor cell proliferation and distant migration and inhibits the killing effect of CAR-T on tumor cells.
Figure 3
Figure 3
Immune checkpoint blockade of T-cell activation.
Figure 4
Figure 4
Manufacturing steps of CAR-T cells.
See this image and copyright information in PMC

References

    1. Sadelain M, Riviere I, Brentjens R. Targeting tumours with genetically enhanced t lymphocytes. Nat Rev Cancer (2003) 3:35–45. doi: 10.1038/nrc971 - DOI - PubMed
    1. Kenderian SS, Ruella M, Gill S, Kalos M. Chimeric antigen receptor t-cell therapy to target hematologic Malignancies. Cancer Res (2014) 74:6383–9. doi: 10.1158/0008-5472.CAN-14-1530 - DOI - PubMed
    1. Mohty M, Dulery R, Gauthier J, Malard F, Brissot E, Aljurf M, et al. Car t-cell therapy for the management of refractory/relapsed high-grade b-cell lymphoma: A practical overview. Bone Marrow Transpl (2020) 55:1525–32. doi: 10.1038/s41409-020-0892-7 - DOI - PubMed
    1. Shi H, Sun ML, Liu L, Wang ZH. Chimeric antigen receptor for adoptive immunotherapy of cancer: Latest research and future prospects. Mol Cancer (2014) 13. doi: 10.1186/1476-4598-13-219 - DOI - PMC - PubMed
    1. Brudno JN, Kochenderfer JN. Chimeric antigen receptor t-cell therapies for lymphoma. Nat Rev Clin Oncol (2018) 15:31–46. doi: 10.1038/nrclinonc.2017.128 - DOI - PMC - PubMed

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