Accession Number:

ADA459722

Title:

Glycopetide-Based Immunotherapy for Prophylaxis and Treatment of Mammary Adenocarcinomas

Descriptive Note:

Final rept. 1 Sep 2002-31 May 2006

Corporate Author:

CALIFORNIA UNIV SAN DIEGO DEPT OF MEDICINE

Personal Author(s):

Report Date:

2006-06-01

Pagination or Media Count:

25.0

Abstract:

This proposal aimed at defining the use of glycopeptides containing tumor associated carbohydrate antigens TACA, that bind multiple MHC class I alleles, as potential preventive vaccines for carcinomas on a large scale. Our recent results JEM 2004 199707, see appendix suggest that CD8 T cells CTL are capable of recognizing TACA in a conventional class I MHC-restricted fashion. TF, a disaccharide, and Tn, its immediate precursor, are TACA largely expressed in carcinomas. TF and Tn can be successfully used as T helper Th-independent vaccines when conjugated to designer peptide with optimal binding affinity for class I MHC molecules. TF- and Tn-specific CTL generated with this strategy are capable of recognizing TACA-expressing tumors in vitro, suggesting that glycopeptides are as effectively presented by class I MHC molecules as non-glycosylated peptides JEM 2004 199707. Because the exact sequences of endogenously synthesized glycopeptides are unknown, the TACA-specific T cell repertoire elicited by carbohydrate-based vaccines is assumed to be degenerate. Here we report that mice genetically manipulated to develop TACA-expressing mammary tumors are not tolerant to glycopeptide vaccination Figures 1 and 2, Immunol and Cell Biol., 2005 83440, see appendix. Moreover, we tested the immunogenicity of designer glycopeptides, capable of binding multiple MHC class I alleles Table 1, Immunol and Cell Biol., 2005 83440, see appendix, as a novel approach for the development of vaccines potentially useful for vaccination of a large fraction of the general population. Our results have suggested that CTL derived from normal donors respond with high efficiency to glycopeptides in vitro, opening a new avenue for the design of prospective vaccines for cancer prevention Table 2, Immunol and Cell Biol., 2005 83440, see appendix.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE