Accession Number : ADA301700

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

Descriptive Note : Annual rept. 1 Sep 94-31 Aug 95,

Corporate Author : ILLINOIS UNIV CHAMPAIGN

Personal Author(s) : Kranz, David M.

PDF Url : ADA301700

Report Date : SEP 1995

Pagination or Media Count : 26

Abstract : 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.

Descriptors :   *ANTIBODIES, *CYTOTOXINS, *T LYMPHOCYTES, *CELLS(BIOLOGY), *MAMMARY GLANDS, *BREAST CANCER, MODELS, HUMANS, NEOPLASMS, REGIONS, TARGETING, GENES, CLONES, ANIMALS, MICE, RANGE(EXTREMES), IN VIVO ANALYSIS, TRANSPLANTATION, LYSIS.

Subject Categories : Medicine and Medical Research
      Anatomy and Physiology

Distribution Statement : APPROVED FOR PUBLIC RELEASE