Bispecific antibodies retarget murine T cell cytotoxicity against syngeneic breast cancer in vitro and in vivo.
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.
Moreno
M B
MB
Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
Titus
J A
JA
Cole
M S
MS
Tso
J Y
JY
Le
N
N
Paik
C H
CH
Bakács
T
T
Zacharchuk
C M
CM
Segal
D M
DM
Wunderlich
J R
JR
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*
D018033:Antibodies, Bispecific; D000957:Antigens, Viral, Tumor; D017260:Receptor-CD3 Complex, Antigen, T-Cell