Vaccination with Tumor-Ganglioside Glycomimetics Activates a Selective Immunity that Affords Cancer Therapy

Cell Chem Biol. 2019 Jul 18;26(7):1013-1026.e4. doi: 10.1016/j.chembiol.2019.03.018. Epub 2019 May 16.

Abstract

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 γδ 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.

Keywords: cancer therapy; ganglioside; glycomimetic; immunity; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / therapeutic use
  • Cell Line, Tumor
  • Female
  • Gangliosides / immunology*
  • Gangliosides / therapeutic use
  • Glycolipids / immunology*
  • Humans
  • Immunity, Cellular / immunology
  • Immunity, Humoral / immunology
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms / immunology
  • Neoplasms / therapy
  • T-Lymphocytes / immunology
  • Vaccination / methods

Substances

  • Antibodies, Monoclonal
  • Cancer Vaccines
  • Gangliosides
  • Glycolipids
  • ganglioside, GD3
  • ganglioside, GD2

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