IMMUNOLOGIC ANALYSIS--MULTIDRUG RESISTANT GENE FAMILY

Project: Research project

Project Details

Description

Resistance to multiple chemotherapeutic agents remains a major
obstacle in successful management of human malignancies.
Recently a specific gene, termed mdr p-glycoprotein, has been
demonstrated to be amplified and overexpressed in multidrug
resistant cell lines. This gene which is a member of a multigene
family has been shown to convey resistance to multiple drugs in
vitro. This proposal is focused on the development of antibodies
to specific epitopes of the polypeptides which make up the mdr p-
glycoprotein family in the mouse and man. The characterization
of these antibodies with respect to specificity for each family
member and the interaction with specific functional sites on the
polypeptide chain will provide essential information for studies on
normal and neoplastic tissues. These antibodies will be essential
in determining the distribution and expression of the mdr p-
glycoprotein in normal tissues and clinically in neoplasms during
chemotherapy. As the role of the mdr p-glycoprotein in the
development of drug resistance is clarified then the potential
application of appropriate monoclonal antibodies for the reversal
of multidrug resistance in vivo will be considered. The specific goals of this project are: 1) generation of antibodies
to the 3 members of the mdr p-glycoprotein gene family, 2)
generate antibodies to specific domains within the different
family members, 3) map the structure of the mdr p-glycoproteins
4) determine the tissue distrimdrn of each of the mdr p-
glycoproteins, 5) determine the role each member of the gene
family in the generation of drug resistance, 6) evaluate functional
domains of the mdr p-glycoprotein family members, 7) screen
human tumors with these antibodies to determine the role of this
gene family in the clinical development of drug resistance.
StatusFinished
Effective start/end date9/1/886/30/93

Funding

  • National Institutes of Health
  • National Institutes of Health: $248,672.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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