Designer glycopeptides for cytotoxic T cell-based elimination of carcinomas.
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 (beta-Gal-[1-->3]-alpha-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.
Torrey Pines Institute for Molecular Studies, 3550 General Atomic Court, San Diego, CA 92121, USA.
Yanfei
Y
Xu
Sandra J
SJ
Gendler
Alessandra
A
Franco
D000595:Amino Acid Sequence; D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry; D019496:Cancer Vaccines / Q000737:chemistry / Q000494:pharmacology*; D002240:Carbohydrate Sequence; D003429:Cross Reactions; D015195:Drug Design; D005260:Female; D006020:Glycopeptides / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology*
D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D006020:Glycopeptides; C016467:Thomsen-Friedenreich antigen