A mimic of tumor rejection antigen-associated carbohydrates mediates an antitumor cellular response.

Abstract

Tumor-associated carbohydrate antigens are typically perceived as inadequate targets for generating tumor-specific cellular responses. Lectin profile reactivity and crystallographic studies demonstrate that MHC class I molecules can present to the immune system posttranslationally modified cytosolic peptides carrying O-beta-linked N-acetylglucosamine (GlcNAc). Here we report that a peptide surrogate of GlcNAc can facilitate an in vivo tumor-specific cellular response to established Meth A tumors that display native O-GlcNAc glycoproteins on the tumor cell surface. Peptide immunization of tumor-bearing mice had a moderate effect on tumor regression. Inclusion of interleukin 12 in the immunization regimen stimulated complete elimination of tumor cells in all of the mice tested, whereas interleukin 12 administration alone afforded no tumor growth inhibition. Adoptive transfer of immune T cells into tumor-bearing nude mice indicates a role for CD8+ T cells in tumor regression. This work postulates that peptide mimetics of glycosylated tumor rejection antigens might be further developed for immune therapy of cancer.

• Authors: Behjatolah Monzavi-Karbassi, Ping Luo, Fariba Jousheghany, Marta Torres-Quiñones, Gina Cunto-Amesty, Cecile Artaud, Thomas Kieber-Emmons
• Journal: Cancer research (Cancer Res) Vol. 64 Issue 6 Pg. 2162-6 (Mar 15 2004) ISSN: 0008-5472 [Print] United States
• PMID: 15026358 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, Tumor-Associated, Carbohydrate
• Histocompatibility Antigens Class I
• Peptide Fragments
• Interleukin-12
• Interferon-gamma
• Acetylglucosamine

Topics

• Acetylglucosamine (immunology)
• Animals
• Antigen Presentation
• Antigens, Tumor-Associated, Carbohydrate (immunology, metabolism, therapeutic use)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cytosol (metabolism)
• Female
• Histocompatibility Antigens Class I (immunology, metabolism)
• Humans
• Immunization
• Immunotherapy
• Interferon-gamma (metabolism)
• Interleukin-12 (therapeutic use)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Molecular Mimicry
• Peptide Fragments (immunology, metabolism, therapeutic use)
• Sarcoma, Experimental (immunology, pathology, prevention & control)
• Spleen (immunology)
• T-Lymphocytes, Cytotoxic (drug effects, immunology)