Chimeric antigen receptor-engineered T cells for immunotherapy of cancer.
CD4+ and CD8+ T lymphocytes are powerful components of adaptive immunity, which essentially contribute to the elimination of tumors. Due to their cytotoxic capacity, T cells emerged as attractive candidates for specific immunotherapy of cancer. A promising approach is the genetic modification of T cells with chimeric antigen receptors (CARs). First generation CARs consist of a binding moiety specifically recognizing a tumor cell surface antigen and a lymphocyte activating signaling chain. The CAR-mediated recognition induces cytokine production and tumor-directed cytotoxicity of T cells. Second and third generation CARs include signal sequences from various costimulatory molecules resulting in enhanced T-cell persistence and sustained antitumor reaction. Clinical trials revealed that the adoptive transfer of T cells engineered with first generation CARs represents a feasible concept for the induction of clinical responses in some tumor patients. However, further improvement is required, which may be achieved by second or third generation CAR-engrafted T cells.
Cartellieri
Marc
M
Institute of Immunology, Medical Faculty, Technical University of Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
Bachmann
Michael
M
Feldmann
Anja
A
Bippes
Claudia
C
Stamova
Slava
S
Wehner
Rebekka
R
Temme
Achim
A
Schmitz
Marc
M
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D018448:Models, Immunological; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D015202:Protein Engineering / Q000379:methods*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D015398:Signal Transduction / Q000276:immunology
D000951:Antigens, Neoplasm; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins
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