Bispecific antibody therapy of two murine B-cell lymphomas.
Numerous in vitro studies have shown that T lymphocytes can be targeted towards any target cell by using bispecific antibodies (bsAbs) with specificity of the CD3/TCR complex and a target cell antigen. We have produced bsAbs directed against the membrane expressed idiotype of the murine B cell lymphomas BCLI and 38C13, and murine CD3 complex. The dual specificity of the hybrid-hybridoma produced monoclonal antibodies (MAbs) could be demonstrated by flow cytometry, the induction of T cell proliferation, the induction of IL2 secretion by polyclonal T cells, and redirected lysis of the relevant target cells. Immunotherapy of tumor bearing animals demonstrated that bsAbs could efficiently target T cells towards the tumor cells, that tumor cell--T cell bridging is established in vivo, and that both T cell subsets contribute to tumor regression resulting in long-term survival and cure of the lymphomas.
Demanet
C
C
Unit of Hematology-Immunology, Vrije Universiteit Brussel (VUB), Belgium.
Brissinck
J
J
Moser
M
M
Leo
O
O
Thielemans
K
K
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity; D003602:Cytotoxicity, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D007167:Immunotherapy / Q000379:methods; D016393:Lymphoma, B-Cell / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured
D000906:Antibodies