Therapy for minimal residual tumor disease: beta-galactosylceramide inhibits the growth of recurrent HPV16-associated neoplasms after surgery and chemotherapy
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
19739073
DOI
10.1002/ijc.24887
Knihovny.cz E-resources
- MeSH
- Ceramides pharmacology MeSH
- Immunotherapy MeSH
- Papillomavirus Infections immunology pathology prevention & control MeSH
- Humans MeSH
- Human papillomavirus 16 isolation & purification MeSH
- Neoplasm Recurrence, Local immunology pathology prevention & control MeSH
- Monosaccharides pharmacology MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Tumor Cells, Cultured transplantation MeSH
- Neoplasm, Residual drug therapy surgery virology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- beta-galactosyl ceramide MeSH Browser
- Ceramides MeSH
- Monosaccharides MeSH
Natural killer T (NKT) cells are potent modulators of antitumor immunity. Their protective effects can be achieved upon their activation by glycolipid ligands presented in the context of the CD1d molecule. These CD1d-binding glycolipid antigens have been described as potent therapeutic agents against tumors, infections, as well as autoimmune diseases. Immunoregulatory and therapeutic effects of glycolipid ligands depend on their structure and modes of administration. Therefore, more studies are needed for optimization of the particular therapeutic settings. This study was focused on the tumor-inhibitory effects of 12 carbon acyl chain beta-galactosyl ceramide (C12 beta-D-Galactosyl Ceramide; beta-GalCer(C12)) on the growth of human papillomavirus type 16 (HPV16)-associated neoplasms transplanted in syngeneic mice. Treatment of tumor-bearing mice with beta-GalCer(C12) 3-14 days after tumor cell transplantation significantly inhibited the growth of the major histocompatibility complex (MHC) Class I-positive (TC-1), as well as MHC Class I-deficient (TC-1/A9) HPV16-associated tumors. Moreover, administration of beta-GalCer(C12) after surgical removal of TC-1 tumors inhibited the growth of tumor recurrences. Similar results were obtained in the treatment of tumors after chemotherapy. beta-GalCer(C12) treatment turned out to be also synergistic with immunotherapy based on administration of IL-12-producing cellular vaccines. These results suggest that beta-GalCer(C12), whose antitumor effects have so far not been studied in detail, can be effective for the treatment of minimal residual tumor disease as well as an adjuvant for cancer immunotherapy.
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