BACKGROUND & AIMS: 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.
BACKGROUND & AIMS: 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.
Authors: A Hombach; C Schlimper; E Sievers; S Frank; H H Schild; T Sauerbruch; I G H Schmidt-Wolf; H Abken Journal: Gut Date: 2005-09-27 Impact factor: 23.059