Immunization of Rhesus monkeys with a SialylTn-mAb17-1A conjugate vaccine co-formulated with QS-21 induces a temporary systemic cytokine release and NK cytotoxicity against tumor cells

Cancer Immunol Immunother. 2007 Jun;56(6):863-73. doi: 10.1007/s00262-006-0231-x. Epub 2006 Sep 29.

Abstract

Tumor-associated antigens resulting from aberrant glycosylation, such as the SialylTn carbohydrate antigen, are frequently over-expressed on cancer cells and provide potential targets for cancer vaccination. Immunization of Rhesus monkeys with SialylTn coupled to a highly immunogenic carrier molecule and formulated on aluminum hydroxide induced a strong immune response against the carrier protein but only a moderate IgM immune response against the SialylTn carbohydrate antigen. Co-formulation with QS-21 adjuvant dramatically enhanced the anti-SialylTn immune response and resulted in a SialylTn-specific IgG switch. The kinetics of the carbohydrate-specific IgG response correlated with a temporary release of cytokines such as IFNgamma, IL-2, IL-1beta, TNFalpha and GM-CSF which was measurable in the immune serum by xMAP Multiplex technology. Furthermore, tumor cell killing by activated natural killer cells was induced. These data demonstrate that immunization with a tumor-associated carbohydrate antigen in a highly immunogenic formulation results in a temporary release of type 1 cytokines which may be required for the induction of a specific IgG immune response against the carbohydrate antigen as well as for activation of effector cells against tumor cells.

MeSH terms

  • Adjuvants, Immunologic*
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antigens, Tumor-Associated, Carbohydrate / immunology*
  • Cancer Vaccines / immunology*
  • Cytokines / blood*
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation / immunology
  • Macaca mulatta
  • Saponins / immunology*
  • Vaccines, Conjugate / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Monoclonal
  • Antigens, Tumor-Associated, Carbohydrate
  • Cancer Vaccines
  • Cytokines
  • Immunoglobulin G
  • Saponins
  • Vaccines, Conjugate
  • saponin QA-21V1