Retargeting of cytolytic T lymphocytes by heteroaggregated (bispecific) antibodies.
The specificity and efficiency of tumor cell lysis by the retargeting of murine and human cytolytic T lymphocytes (CTL) with heteroaggregated (also known as bispecific or hybrid) antibodies were examined. Both murine and human CTL were capable of lysing various tumor cell targets in the presence of low concentrations of an appropriate heteroaggregated antibody. However, CTL (excluding clones) were lytic only when activated using reagents such as concanavalin A and interleukin 2 (IL2) with murine effector cells and with mitogenic mAb with human effector cells. The addition of IL2 (at 50-100 U/ml) did not cause enhanced lysis of the target cells used in the presence of heteroaggregated antibody with the murine effector cells. Furthermore, the lysis of target cells by heteroaggregated antibodies and CTL did not cause the lysis of bystander cells (cells not expressing an antigen recognized by the antibody that are mixed with the target cells). The efficient CTL-mediated lysis observed with these antibodies makes this a promising approach for the immunotherapy of human cancer.
Barr
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Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland.
Buchegger
F
F
MacDonald
H R
HR
Carrel
S
S
von Fliedner
V
V
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D003208:Concanavalin A / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors
D000906:Antibodies; D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D003208:Concanavalin A