Tong et al. generated lipid-free ganglioside mimetics that are structurally identical to native GD2 and GD3, and showed that when used as vaccines, these molecules elicit humoral and cellular antigen-specific immune responses in tumor-bearing mice. The vaccine or adoptive transfer of T cells from vaccinated donors reduced the volume of primary tumors in prophylactic and therapeutic settings and prolonged survival in several murine tumor models. Mechanistically, the vaccine expanded the number of γδ and CD8+ T cells in the spleen, lymph nodes, and tumor. No side effects were observed.
Immune targeting of (glyco)protein tumor markers has been useful to develop cancer and virus vaccines. However, the ganglioside family of tumor-associated glycolipids remains intractable to vaccine approaches. Here we show that synthetic antigens mimicking the carbohydrate moiety of GD2 or GD3 gangliosides can be used as vaccines to activate a selective humoral and cellular immunity that is therapeutic against several cancers expressing GD2 or GD3. Adoptive transfer of T cells generated after vaccination elicits tumor-infiltrating lymphocytes of the gammadelta T cell receptor and CD8(+) phenotypes; and affords a high therapeutic index. The glycomimetic vaccine principles can be expanded to target the family of tumor gangliosides and other carbohydrates expressed primarily in pathological states.
Author Info: (1) Lady Davis Institute-Jewish General Hospital, 3755 Cote St. Catherine, E-535, Montreal, QC H3T 1E2, Canada; Pharmacology and Therapeutics, McGill University, Montreal, QC H3G 1
Author Info: (1) Lady Davis Institute-Jewish General Hospital, 3755 Cote St. Catherine, E-535, Montreal, QC H3T 1E2, Canada; Pharmacology and Therapeutics, McGill University, Montreal, QC H3G 1Y6, Canada. (2) Lady Davis Institute-Jewish General Hospital, 3755 Cote St. Catherine, E-535, Montreal, QC H3T 1E2, Canada. (3) Lady Davis Institute-Jewish General Hospital, 3755 Cote St. Catherine, E-535, Montreal, QC H3T 1E2, Canada. (4) Lady Davis Institute-Jewish General Hospital, 3755 Cote St. Catherine, E-535, Montreal, QC H3T 1E2, Canada. (5) Lady Davis Institute-Jewish General Hospital, 3755 Cote St. Catherine, E-535, Montreal, QC H3T 1E2, Canada. (6) Human Health Therapeutics Research Centre, National Research Council of Canada, Ottawa K1A 0R6, Canada. (7) Human Health Therapeutics Research Centre, National Research Council of Canada, Ottawa K1A 0R6, Canada. (8) Lady Davis Institute-Jewish General Hospital, 3755 Cote St. Catherine, E-535, Montreal, QC H3T 1E2, Canada. (9) Lady Davis Institute-Jewish General Hospital, 3755 Cote St. Catherine, E-535, Montreal, QC H3T 1E2, Canada; Pharmacology and Therapeutics, McGill University, Montreal, QC H3G 1Y6, Canada. (10) Lady Davis Institute-Jewish General Hospital, 3755 Cote St. Catherine, E-535, Montreal, QC H3T 1E2, Canada. (11) Lady Davis Institute-Jewish General Hospital, 3755 Cote St. Catherine, E-535, Montreal, QC H3T 1E2, Canada; Pharmacology and Therapeutics, McGill University, Montreal, QC H3G 1Y6, Canada. Electronic address: uri.saragovi@mcgill.ca.
