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T Cell Receptors for Gene Transfer in Adoptive T Cell Therapy
被引:3
作者:
Sharma, Preeti
[1
]
Kranz, David M.
[1
]
机构:
[1] Univ Illinois, Dept Biochem, Urbana, IL 61801 USA
关键词:
T cell receptor;
cancer;
adoptive T cell therapy;
clinical trials;
MHC-CLASS-I;
CANCER REGRESSION;
NEGATIVE SELECTION;
ANTITUMOR-ACTIVITY;
BINDING-AFFINITY;
CROSS-REACTIVITY;
TUMOR-ANTIGENS;
TCR;
PEPTIDE;
LYMPHOCYTES;
D O I:
10.1615/CritRevImmunol.2019030788
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
摘要:
The past decade has seen enormous progress in cancer immunotherapy. Checkpoint inhibitors are a class of immunotherapy that act to recruit endogenous T cells of a patient's immune system against cancer-associated peptide-MHC antigens. In this process, mutated antigenic peptides referred to as neoantigens often serve as the target on cancer cells that are recognized by the T cell receptor (TCR) on endogenous T cells. Another successful immunotherapy has involved adoptive T cell therapy, where therapeutic doses of T cells expressing a gene for an anti-cancer receptor are delivered to a patient. This approach has been used primarily against hematopoietic cancers using synthetic receptors called chimeric antigen receptors (CARs). CARs typically contain an antibody fragment (single-chain Fv, scFv) against a cancer cell surface antigen such as the B cell molecule CD19. While therapeutic CARs (and full antibodies) target antigens expressed on cell surfaces, TCRs can target a much larger array of intracellular proteins by binding to any cellular peptide associated with an MHC product. These cancer targets include self-peptides from aberrantly expressed/overexpressed proteins or neoantigens. In this review, we discuss the use of TCRs in adoptive T cell therapy and their target antigens. We focus on two properties that impact sensitivity, potency, and possible toxic cross-reactivity of TCR-mediated therapy: (1) the affinity of the TCR for the target antigen, and (2) the density of the target antigen. Finally, we provide a comprehensive listing of the current clinical trials that involve TCRs in adoptive T cell cancer therapy.
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页码:105 / 122
页数:18
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