title: Bispecific antibodies retarget murine T cell cytotoxicity against syngeneic breast cancer in vitro and in vivo.
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 synergeic 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 epsilon-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 retargeting T cells with bispecific antibodies against syngeneic breast cancer.
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Moreno
authors.forename: J A
authors.initials: JA
authors.lastname: Titus
authors.forename: M S
authors.initials: MS
authors.lastname: Cole
authors.forename: J Y
authors.initials: JY
authors.lastname: Tso
authors.forename: N
authors.initials: N
authors.lastname: Le
authors.forename: C H
authors.initials: CH
authors.lastname: Paik
authors.forename: T
authors.initials: T
authors.lastname: Bakács
authors.forename: C M
authors.initials: CM
authors.lastname: Zacharchuk
authors.forename: D M
authors.initials: DM
authors.lastname: Segal
authors.forename: J R
authors.initials: JR
authors.lastname: Wunderlich
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology*; D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology*; D000957:Antigens, Viral, Tumor / Q000032:analysis / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology*; D008324:Mammary Tumor Virus, Mouse / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D018033:Antibodies, Bispecific; D000957:Antigens, Viral, Tumor; D017260:Receptor-CD3 Complex, Antigen, T-Cell