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Cancer Immunology, Immunotherapy : CII logoLink to Cancer Immunology, Immunotherapy : CII
. 1995 May;40(3):182–190. doi: 10.1007/BF01517350

Bispecific antibodies retarget murine T cell cytotoxicity against syngeneic breast cancer in vitro and in vivo

M Belen Moreno 1,2, Julie A Titus 1, Michael S Cole 3, J Yun Tso 3, Nhat Le 4, Chang H Paik 4, Tibor Bakács 1, Charles M Zacharchuk 2, David M Segal 5,✉, John R Wunderlich 1
PMCID: PMC11037834  PMID: 7728777

Abstract

Bispecific antibodies with specificity for CD3 and a tumor antigen can redirect cytolytic T cells to kill tumor targets, regardless of their natural specificity. To assess the clinical potential of bispecific antibodies for treatment of human cancers we have, in the present study, adapted a totally syngeneic mouse model to the targeting of mouse T cells against mouse tumors in immunocompetent mice. We show that gp52 of the mouse mammary tumor virus (MTV) can serve as a tumor-specific antigen for redirected cellular cytotoxicity. Chemically crosslinked and genetically engineered bispecific antibodies with specificities for gp52 and murine CD3 ε-chain induced activated mouse T cells to specifically lyse mouse mammary tumor cells from cultured lines and primary tumors from C3H-MTV+ mice. Retargeted T cells also blocked the growth of mammary tumors in vitro as well as their growth in syngeneic mice. These findings identify murine MTV-induced mammary adenocarcinomas as a solid-tumor, animal model for retargetin T cells with bispecific antibodies against syngeneic breast cancer.

Key words: Bispecific antibody, Redirected lysis, Targeted cytotoxicity, Mammary tumor, Mouse model

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