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Review
. 2022 Jan 25:11:794183.
doi: 10.3389/fonc.2021.794183. eCollection 2021.

TCR-T Immunotherapy: The Challenges and Solutions

Yating Liu  1   2 , Xin Yan  2 , Fan Zhang  2 , Xiaoxia Zhang  2 , Futian Tang  2 , Zhijian Han  2 , Yumin Li  2
Affiliations
Review

TCR-T Immunotherapy: The Challenges and Solutions

Yating Liu et al. Front Oncol. .

Abstract

T cell receptor-engineered T cell (TCR-T) therapy is free from the limit of surface antigen expression of the target cells, which is a potential cellular immunotherapy for cancer treatment. Significant advances in the treatment of hematologic malignancies with cellular immunotherapy have aroused the interest of researchers in the treatment of solid tumors. Nevertheless, the overall efficacy of TCR-T cell immunotherapy in solid tumors was not significantly high when compared with hematological malignancies. In this article, we pay attention to the barriers of TCR-T cell immunotherapy for solid tumors, as well as the strategies affecting the efficacy of TCR-T cell immunotherapy. To provide some reference for researchers to better overcome the impact of TCR-T cell efficiency in solid tumors.

Keywords: challenges; immunotherapy; receptor-engineered T cell; solid tumors; solutions.

PubMed Disclaimer

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
Schematic diagram of the TCR-T cell structure. The TCR complex is a heterodimer consisting of two different peptide chains. The MHC class 1 present intracellular antigenic peptides of cancer cells for recognition by the T cell receptor, and surround by CD28 and B7.
Figure 2
Figure 2
Reducing mismatches between endogenous and heterogeneous TCR and reducing competition for CD3 molecules can mediate an increase in surface expression of modified TCR cells.
Figure 3
Figure 3
RAG2 knockout by CRISPR-based genome editing in T-iPSCs prevents the additional TCR rearrangement.
Figure 4
Figure 4
After T cells interact with MHC through TCR, several proteins will be recruited to the plasma membrane to participate in signal transduction.
See this image and copyright information in PMC

References

    1. Rosenberg SA, Restifo NP. Adoptive Cell Transfer as Personalized Immunotherapy for Human Cancer. Science (2015) 348(6230):62–8. doi: 10.1126/science.aaa4967 - DOI - PMC - PubMed
    1. Fesnak AD, June CH, Levine BL. Engineered T Cells: The Promise and Challenges of Cancer Immunotherapy. Nat Rev Cancer (2016) 16(9):566–81. doi: 10.1038/nrc.2016.97 - DOI - PMC - PubMed
    1. Zhao Q, Jiang Y, Xiang S, Kaboli PJ, Shen J, Zhao Y, et al. . Engineered TCR-T Cell Immunotherapy in Anticancer Precision Medicine: Pros and Cons. Front Immunol (2021) 12:658753. doi: 10.3389/fimmu.2021.658753 - DOI - PMC - PubMed
    1. Wei SC, Duffy CR, Allison JP. Fundamental Mechanisms of Immune Checkpoint Blockade Therapy. Cancer Discovery (2018) 8(9):1069–86. doi: 10.1158/2159-8290.CD-18-0367 - DOI - PubMed
    1. Stromnes IM, Schmitt TM, Chapuis AG, Hingorani SR, Greenberg PD. Re-Adapting T Cells for Cancer Therapy: From Mouse Models to Clinical Trials. Immunol Rev (2014) 257(1):145–64. doi: 10.1111/imr.12141 - DOI - PMC - PubMed

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