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Review
. 2020 Jun:49:101437.
doi: 10.1016/j.smim.2020.101437. Epub 2020 Nov 29.

Adoptive T cell therapy: Boosting the immune system to fight cancer

Ernesto Leon  1 , Raghuveer Ranganathan  2 , Barbara Savoldo  3
Affiliations
Review

Adoptive T cell therapy: Boosting the immune system to fight cancer

Ernesto Leon et al. Semin Immunol. 2020 Jun.

Abstract

Cellular therapies have shown increasing promise as a cancer treatment. Encouraging results against hematologic malignancies are paving the way to move into solid tumors. In this review, we will focus on T-cell therapies starting from tumor infiltrating lymphocytes (TILs) to optimized T-cell receptor-modified (TCR) cells and chimeric antigen receptor-modified T cells (CAR-Ts). We will discuss the positive preclinical and clinical findings of these approaches, along with some of the persisting barriers that need to be overcome to improve outcomes.

Keywords: Adoptive cell therapy; CAR-T cells; Cytolytic T cells (CTLs); Hematologic malignancies; T-cell receptor-modified (TCR) cells; Tumor infiltrating T cells (TILs).

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Figures

Figure 1.
Figure 1.
Overview of the adoptive cell therapy (ACT) process for cancer treatment using tumor-infiltrating lymphocytes (TILs), cytotoxic T lymphocytes (CTL), or genetically modified TCR-T or CAR-T cells. A. For TIL ACT, tumors are resected, and tumor-reactive T cells are isolated and expanded ex vivo. B. CTL therapy relies on enriching and expanding peripheral blood T cells with known TAA specificity. C & D. ACT with TCR-T or CAR-T cells relies on the genetic modification of peripheral blood T cells by viral vectors to express a specific TCR or CAR. Patients are pretreated with a lymphodepletion regime before adoptive transfer of TILs, TCR-T, or CAR-T cells to create space and availability of homeostatic and activating cytokines. Figure created with Biorender.
Figure 2.
Figure 2.
Schematic representation of CAR T cell control mechanisms. A. Tuning the affinity of the scFv to tumor antigen and drug-induced inhibition of CAR T cell signaling by dasatinib. B. Split-CAR signaling by adaptors or drug-induced dimerization. HIF-driven CAR expression is regulated by hypoxic environment i.e. tumor microenvironment. The suicide gene iCasp9 can be activated by a dimerizable drug to kill CAR T cells. C. CAR T cells can have autonomous regulation in the killing of targets based on cell surface protein expression by cancerous and healthy cells. Figure created with Biorender.
Figure 3.
Figure 3.
History of adoptive cell therapy (ACT) in cancer. This timeline highlights important developments in the field of adoptive T-cell therapy. Figure created with Biorender.
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References

    1. Rosenberg SA, Spiess P, Lafreniere R, A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes, Science (80-.). 233 (1986) 1318–1321. 10.1126/science.3489291. - DOI - PubMed
    1. Romieu R, Baratin M, Kayibanda M, Lacabanne V, Ziol M, Guillet JG, Viguier M, Passive but not active CD8+ T cell-based immunotherapy interferes with liver tumor progression in a transgenic mouse model, J. Immunol 161 (1998) 5133–517. - PubMed
    1. Krogsgaard M, Davis MM, How T cells “see” antigen, Nat. Immunol 6 (2005) 239–245. 10.1038/ni1173. - DOI - PubMed
    1. Lauss M, Donia M, Harbst K, Andersen R, Mitra S, Rosengren F, Salim M, Vallon-Christersson J, Törngren T, Kvist A, Ringnér M, Svane IM, Jönsson G, Mutational and putative neoantigen load predict clinical benefit of adoptive T cell therapy in melanoma, Nat. Commun 8 (2017) 1–11. 10.1038/s41467-017-01460-0. - DOI - PMC - PubMed
    1. Jha S, Rollins MG, Fuchs G, Procter DJ, Hall EA, Cozzolino K, Sarnow P, Savas JN, Walsh D, Mining Exomic Sequencing Data to Identify Mutated Antigens Recognized by Adoptively Transferred Tumor-reactive T cells, Nat. Med 546 (2017) 651–655. 10.1038/nature22814.Trans-kingdom. - DOI

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