Accession Number:

ADB247842

Title:

Stimulating CTL Towards HER2/neu Overexpressing Breast Cancer

Descriptive Note:

Annual rept. 30 Sep 1997-29 Sep 1998

Corporate Author:

NORTH CAROLINA UNIV AT CHAPEL HILL

Personal Author(s):

Report Date:

1998-10-01

Pagination or Media Count:

21.0

Abstract:

Most cancer treatments have severe side effects and do not protect against recurrences of the same tumor. We propose to establish an approach by which tumor cells are eradicated through selective induction of CD8 T cells. Our model system will be the tyrosine kinase HER2neu that is overexpressed in 30 of breast and ovarian tumors. A peptide derived from HER2neu HN654-662 has been shown to bind to HLA-A2.1 and stimulate cytotoxic T lymphocytes CTL that lyse primary tumors from ovarian or breast cancer. Therapies have been proposed that utilize this peptide, but the peptide has poor immunogenicity when compared to viral peptides. We have data demonstrating HN654-662 is an extremely poor HLA-A2.1 binding peptide. In a novel approach, we will make use of biophysical techniques that have recently improved sufficiently to use for experimentation. To make HN654-662 an effective therapeutic agent, we propose to first assess how the peptide binds by x-ray crystallography. The crystallographic structure will be used to design altered HN654-662 that increase binding affinity. We propose that some peptides that show increased affinity for HLA-A2.1 will also show increased affinity or avidity for a TCR specific for HLA-A2.1HN654-662 and that these are the best candidates for therapies.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research
  • Crystallography
  • Nuclear Physics and Elementary Particle Physics

Distribution Statement:

APPROVED FOR PUBLIC RELEASE