Characterization of New Breast Tumor-Specific Antigens Using a Novel Antigen Discovery System

Abstract

We have devised a novel tumor antigen discovery system that utilizes dendritic cells (DCs) as antigen presenting cells to prime naive T cells against peptides and proteins isolated from an epithelial tumor (MS) that does not express the known breast tumor-specific antigens, MUC-1 and Her-2/neu. We have extracted peptides from the HLA Class I molecules of the tumor, fractionated the peptides by reverse-phase HPLC (RP-HPLC), and loaded onto DCs to prime naive CD8(+) T cells. Our results showed that 12 of the 65 individual CD8(+) T cell cultures recognized the original tumor. Further analysis of the positive fractions by electrospray mass spectrometry yielded 8 peptide candidates. We are in the process of acquiring the amino acid sequences of these peptides. We have also fractionated protein extracts of the tumor by RP-HPLC and loaded onto DCs to prime naive CD4(+) T cells. Our first attempt yielded an immunostimulatory fraction that contained predominantly two proteins of 17 kD and 19 kD. We have repeated this process, and our results showed 12 of the 52 individual CD4(+) T cell cultures recognized the original tumor. We are in the process of characterizing the identity of these positive protein fractions.

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Document Details

Document Type
Technical Report
Publication Date
Jun 01, 1999
Accession Number
ADA374234

Entities

People

  • Henry Kao

Organizations

  • University of Pittsburgh

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Breast Cancer
  • Cell Line
  • Cells
  • Culture Techniques
  • Lymphocytes
  • Mass Spectrometers
  • Mass Spectrometry
  • Materials
  • Molecules
  • Neoplasms
  • Sequences
  • Spectrometry

Fields of Study

  • Biology

Readers

  • Analytical Chemistry
  • Immunology