T cell targeting of TAG72+ tumor cells by a chimeric receptor with antibody-like specificity for a carbohydrate epitope.
OBJECTIVE
Chimeric receptors with specificity for defined tumor antigens are valuable tools for targeting cytolytic T cells specifically to tumor cells. The aim of this study, for the situation of gastrointestinal cancer, was to investigate the generation of a chimeric T cell receptor that specifically binds the tumor antigen TAG72 (CA72-4) and transmits a signal for cellular activation.


METHODS
A single-chain antibody (scFv) was derived from the monoclonal anti-TAG72 antibody B72.3 by phage display techniques (B72.3-scFv) and fused to the signaling unit of the Fc epsilon-RI receptor gamma chain, resulting in a chimeric signaling receptor, B72.3-scFv-gamma.


RESULTS
The B72.3-scFv and the chimeric B72.3-scFv-gamma receptor bound specifically to the TAG72 antigen. After transfection, T cells expressing the chimeric B72.3-scFv-gamma specifically recognized TAG72 positive cells. Cross-linking of the chimeric receptor with antigen resulted in interleukin 2 release and cytolytic activity against TAG72 positive tumor cells in vitro.


CONCLUSIONS
T cells equipped with the chimeric anti-TAG72 receptor can be specifically activated to target and lyse TAG72 positive gastrointestinal tumor cells.
Hombach
A
A
Klinik I für Innere Medizin, Universität zu Köln, Germany.
Heuser
C
C
Sircar
R
R
Tillmann
T
T
Diehl
V
V
Kruis
W
W
Pohl
C
C
Abken
H
H
D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D006023:Glycoproteins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000276:immunology*; D017455:Receptors, IgE / Q000096:biosynthesis / Q000276:immunology; D017452:Receptors, IgG / Q000096:biosynthesis / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D006023:Glycoproteins; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D017455:Receptors, IgE; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; C047052:tumor-associated antigen 72