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¹ Torrey Pines Institute for Molecular Studies, San Diego, CA 92121
² Mayo Clinic Scottsdale, Scottsdale, AZ 85259

Address correspondence to Alessandra Franco, Torrey Pines Institute for Molecular Studies, 3550 General Atomic Court, San Diego, CA 92121. Phone: (858) 455-3885; Fax: (858) 909-5117; email: afranco{at}tpims.org

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 (ß-Gal-[13]--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.

Key Words: tumor-associated carbohydrate antigens • glycopeptides • CTL • carcinomas • immunotherapy

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