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The Journal of Immunology, Vol 147, Issue 3 1091-1097, Copyright © 1991 by American Association of Immunologists

ARTICLES

Treatment of murine B cell lymphoma with bispecific monoclonal antibodies (anti-idiotype x anti-CD3)

C Demanet, J Brissinck, M Van Mechelen, O Leo and K Thielemans
Unit of Hematology-Immunology, Medical School, Vrije Universiteit Brussel (VUB), Belgium.

It has previously been reported that T lymphocytes can be targeted by using bispecific antibodies consisting of anti-target antibody and anti- CD3. In the present study, a bispecific mAb was developed by somatic hybridization of mouse hybridomas, one producing a mAb against the Id determinant of the mouse B cell lymphoma 38C13 and the other a mAb against a polymorphic determinant on murine CD3. The bispecific antibody, anti-38C13 x anti-CD3, is bi-isotypic (IgG1 x IgG2a) and was purified by ion exchange and affinity chromatography. The dual specificity of the hybrid hybridoma-produced mAb could be demonstrated by flow cytometry, the induction of T cell proliferation, the induction of IL-2 secretion by polyclonal T cells, and redirected lysis of the relevant target cells. The hybrid (bi-isotypic) Fc part of the bispecific antibodies was nonfunctional in FcR-dependent redirected lysis. In vivo studies demonstrate that this bispecific mAb could efficiently target T cells towards the tumor cells, resulting in long term survival and cure of the lymphoma.


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