Research / Clinical Summary

Alessandra Franco, MD, PhD Assistant Adjunct Professor, Pediatrics Cancer Biology Program Contact by Email

Dr. Franco's laboratory defined that CD8+ cytotoxic T cells (CTL) recognize sugars in association with class I molecules of the major histocompatibility complex (MHC) when presented in the context of peptide backbones. In fact, CTL are capable of recognizing tumor-associated carbohydrate antigens (TACA) linked to designer glycopeptides with high affinity for class I MHC molecules in mice and humans. TACA-containing glycopeptides result in superagonistic epitopes, which are more immunogenic than corresponding peptides.

Franco's lab targeted the Thomsen-Freidenreich (TF) antigen, a disaccharide, and Tn, its immediate precursor, because they are largely expressed in several epithelial tumors, suggesting that the same vaccines can generate sustained CTL responses, potentially capable of preventing/treating a variety of carcinomas.

In support of this “pan-carcinomas” vaccine strategy to prevent/treat tumors in a large scale, glycopeptides with optimal class I MHC binding affinity generate in vivo primary and memory TACA-specific CTL in the absence of T cell help. These CTL kill a variety of carcinomas expressing the TACA molecule.

Most recent studies in healthy human donors consolidate the notion that TACA-containing glycopeptides can efficiently generate carbohydrate-specific CTL in a Th-independent fashion. Franco and her colleagues are currently optimizing the peptide backbone design aiming at phase 1 clinical trials.

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