Bispecific antibodies retarget murine T cell cytotoxicity against syngeneic breast cancer in vitro and in vivo |
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| Authors: | M Belen Moreno Julie A Titus Michael S Cole J Yun Tso Nhat Le Chang H Paik Tibor Bakács Charles M Zacharchuk David M Segal John R Wunderlich |
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| Institution: | (1) Experimental Immunology Branch, The National Cancer Institute, 20892 Bethesda, MD, USA;(2) Laboratory of Immune Cell Biology, The National Cancer Institute, 20892 Bethesda, MD, USA;(3) Protein Design Labs Inc., 940431 Mountain View, CA, USA;(4) Department of Nuclear Medicine, Clinical Center, NIH, 20892 Bethesda, MD, USA;(5) NIH, Building 10, Room 4B17, 20892-1360 Bethesda, MD, USA |
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| 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  -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. |
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| Keywords: | Bispecific antibody Redirected lysis Targeted cytotoxicity Mammary tumor Mouse model |
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