Chimeric antigen receptors for T-cell based therapy.
The Chimeric Antigen Receptor (CAR) consists of an antibody-derived targeting domain fused with T-cell signaling domains that, when expressed by a T-cell, endows the T-cell with antigen specificity determined by the targeting domain of the CAR. CARs can potentially redirect the effector functions of a T-cell towards any protein and nonprotein target expressed on the cell surface as long as an antibody or similar targeting domain is available. This strategy thereby avoids the requirement of antigen processing and presentation by the target cell and is applicable to nonclassical T-cell targets like carbohydrates. This circumvention of HLA-restriction means that the CAR T-cell approach can be used as a generic tool broadening the potential of applicability of adoptive T-cell therapy. Proof-of-principle studies focusing upon the investigation of the potency of CAR T-cells have primarily focused upon the genetic modification of human and mouse T-cells for therapy. This chapter focuses upon methods to modify T-cells from both species to generate CAR T-cells for functional testing.
Cell Therapy Group, Department of Medical Oncology, School of Cancer and Enabling Sciences, Manchester Academic Health Science Center, The University of Manchester, Manchester, UK.
Eleanor J
EJ
Cheadle
Vicky
V
Sheard
Andreas A
AA
Hombach
Markus
M
Chmielewski
Tobias
T
Riet
Cor
C
Berrevoets
Erik
E
Schooten
Cor
C
Lamers
Hinrich
H
Abken
Reno
R
Debets
David E
DE
Gilham
D000818:Animals; D000906:Antibodies / Q000276:immunology; D049109:Cell Proliferation; D002469:Cell Separation; D018274:Electroporation; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D008863:Microspheres; D012313:RNA / Q000378:metabolism; D011946:Receptors, Antigen / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology*; D012190:Retroviridae / Q000502:physiology; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology; D014158:Transcription, Genetic; D014161:Transduction, Genetic; D014162:Transfection
D000906:Antibodies; D011946:Receptors, Antigen; D011994:Recombinant Proteins; D012313:RNA