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.
引用
收藏
页码:105 / 122
页数:18
相关论文
共 104 条
[1]   Different affinity windows for virus and cancer-specific T-cell receptors: Implications for therapeutic strategies [J].
Aleksic, Milos ;
Liddy, Nathaniel ;
Molloy, Peter E. ;
Pumphrey, Nick ;
Vuidepot, Annelise ;
Chang, Kyong-Mi ;
Jakobsen, Bent K. .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2012, 42 (12) :3174-3179
[2]   PRAME-Specific Allo-HLA-Restricted T Cells with Potent Antitumor Reactivity Useful for Therapeutic T-Cell Receptor Gene Transfer [J].
Amir, Avital L. ;
van der Steen, Dirk M. ;
van Loenen, Marleen M. ;
Hagedoorn, Renate S. ;
de Boer, Renate ;
Kester, Michel D. G. ;
de Ru, Arnoud H. ;
Lugthart, Gert-Jan ;
van Kooten, Cees ;
Hiemstra, Pieter S. ;
Jedema, Inge ;
Griffioen, Marieke ;
van Veelen, Peter A. ;
Falkenburg, J. H. Frederik ;
Heemskerk, Mirjam H. M. .
CLINICAL CANCER RESEARCH, 2011, 17 (17) :5615-5625
[3]   CD4 and CD8 binding to MHC molecules primarily acts to enhance Lck delivery [J].
Artyomov, Maxim N. ;
Lis, Mieszko ;
Devadas, Srinivas ;
Davis, Mark M. ;
Chakraborty, Arup K. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (39) :16916-16921
[4]   High-Throughput Stability Screening of Neoantigen/HLA Complexes Improves Immunogenicity Predictions [J].
Blaha, Dylan T. ;
Anderson, Scott D. ;
Yoakum, Daniel M. ;
Hager, Marlies V. ;
Zha, Yuanyuan ;
Gajewski, Thomas F. ;
Kranz, David M. .
CANCER IMMUNOLOGY RESEARCH, 2019, 7 (01) :50-61
[5]   Targeting cancer-specific mutations by T cell receptor gene therapy [J].
Blankenstein, Thomas ;
Leisegang, Matthias ;
Uckert, Wolfgang ;
Schreiber, Hans .
CURRENT OPINION IN IMMUNOLOGY, 2015, 33 :112-119
[6]   Pathways of Antigen Processing [J].
Blum, Janice S. ;
Wearsch, Pamela A. ;
Cresswell, Peter .
ANNUAL REVIEW OF IMMUNOLOGY, VOL 31, 2013, 31 :443-473
[7]   TCRs Used in Cancer Gene Therapy Cross-React with MART-1/Melan-A Tumor Antigens via Distinct Mechanisms [J].
Borbulevych, Oleg Y. ;
Santhanagopolan, Sujatha M. ;
Hossain, Moushumi ;
Baker, Brian M. .
JOURNAL OF IMMUNOLOGY, 2011, 187 (05) :2453-2463
[8]   Affinity-enhanced T-cell receptors for adoptive T-cell therapy targeting MAGE-A10: strategy for selection of an optimal candidate [J].
Border, Ellen C. ;
Sanderson, Joseph P. ;
Weissensteiner, Thomas ;
Gerry, Andrew B. ;
Pumphrey, Nicholas J. .
ONCOIMMUNOLOGY, 2019, 8 (02)
[9]   Impact of negative selection on the T cell repertoire reactive to a self-peptide: A large fraction of T cell clones escapes clonal deletion [J].
Bouneaud, C ;
Kourilsky, P ;
Bousso, P .
IMMUNITY, 2000, 13 (06) :829-840
[10]   The density of peptides displayed by dendritic cells affects immune responses to human tyrosinase and gp100 in HLA-A2 transgenic mice [J].
Bullock, TNJ ;
Colella, TA ;
Engelhard, VH .
JOURNAL OF IMMUNOLOGY, 2000, 164 (05) :2354-2361