Targeted cellular immunotherapy with bifunctional antibodies.
Linking an antitumor cell antibody with an antilymphocyte antibody produces a bifunctional antibody that can redirect T lymphocytes to lyse tumor cells. Bifunctional antibodies that bypass the normal specificity of the T cell antigen receptor can, theoretically, retarget all of a cancer patient's cytotoxic T lymphocytes to kill tumor cells. Studies have demonstrated that bifunctional antibodies redirect effector cells to lyse human tumor cells in vitro and neutralize human tumor xenografts in animal models. Several different effector cell populations have been studied and many different human tumors have been targeted for lysis. Current research goals include the improvement of methods for the preparation of antibody reagents and the enhancement of cellular trafficking to tumors.
Nelson
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Department of Surgery, Mayo Foundation, Rochester, Minnesota 55905.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000627:therapeutic use*; D000918:Antibody Specificity; D000920:Antibody-Dependent Cell Cytotoxicity; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017252:CD3 Complex; D002634:Chemotaxis, Leukocyte; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011961:Receptors, Fc / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000276:immunology
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D011961:Receptors, Fc