Abstract
Tumors express embryonic carbohydrate antigens called tumor-associated carbohydrate antigens (TACA). TACA-containing glycopeptides are appealing cytotoxic T cell (CTL)-based vaccines to prevent or treat cancer because the same sugar moieties are expressed in a variety of tumors, rendering a vaccination strategy applicable in a large population. Here we demonstrate that by using glycopeptides with high affinity for the major histocompatibility complex and glycosylated in a position corresponding to a critical T cell receptor (TcR) contact, it is possible to induce anti-TACA CTL in vivo. In the current study we show that designer glycopeptides containing the Thomsen-Freidenreich (TF) antigen (β-Gal-[1→3]-α -GalNAc-O-serine) are immunogenic in vivo and generate TF-specific CTL capable of recognizing a variety of tumor cells in vitro including a MUC1-expressing tumor. The fine specificity of the TF-specific CTL repertoire indicates that the TcR recognize the glycosylated amino acid residue together with TF in a conventional major histocompatibility complex class I-restricted fashion. These results have high potential for immunotherapy against a broad range of tumors.
Original language | English (US) |
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Pages (from-to) | 707-716 |
Number of pages | 10 |
Journal | Journal of Experimental Medicine |
Volume | 199 |
Issue number | 5 |
DOIs | |
State | Published - Mar 1 2004 |
Keywords
- CTL
- Carcinomas
- Glycopeptides
- Immunotherapy
- Tumor-associated carbohydrate antigens
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology