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Engineering Bispecific Antibodies that Target ERBB-2 on Breast Cancer Cells.

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Annual rept. 1 Sep 94-31 Aug 95,

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The goals of this project are to construct single-chain bispecific antibodies that target erbB-2 on breast cancer cells, to evaluate the susceptibility of the tumor cells to lysis mediated by bispecific antibodies and cytotoxic T cells CTL, and to develop an animal model that can evaluate the in vivo effectiveness of these agents. The following aims were accomplished during the past year. 1 V region genes that encode the anti-erbB-2 antibody 800E6 were cloned by PCR and expressed as a single-chain Fv in E. coli. The scFV-8OOE6 had an affinity for erbB-2 that was nearly identical to the parental antibody. 2 Evaluation of various human breast cancer lines for their ability to be lysed by CTL showed that there is a wide range of intrinsic susceptibilities. The most resistant tumor, SKBR3, was considerably more susceptible to killing when incubated with a combination of TNF-u and IFN-y. 3 Progress was made on establishing a colony of immunodeficient mice that contain an endogenous population of CTL for in vivo targeting of transplanted human tumors. These mice express mouse TCR trans genes but have the recombinational activation gene RAG-1 knocked out.

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  • Medicine and Medical Research
  • Anatomy and Physiology

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