PMID: 11926165Apr 3, 2002Paper

Effective immunotherapy of cancer in MUC1-transgenic mice using clonal cytotoxic T lymphocytes directed against an immunodominant MUC1 epitope

Journal of Immunotherapy
L C HeukampRienk Offringa

Abstract

The tumor-associated autoantigen MUCI is intensively studied as a potential target for antigen-specific immunotherapy of cancer. Previous reports concerning experiments in preclinical murine tumor models have provided evidence supporting the feasibility of this approach. However, such studies have not been performed with clonal cytotoxic T lymphocyte populations displaying a highly defined MUC1 specificity. The authors demonstrate that the immunodominant MUC1-specific cytotoxic T lymphocyte response in C57BL/6 mice is directed against an H-2Kb-restricted epitope, MUC1(19-27), which is derived from the N-terminal signal sequence of the MUC1 protein. Processing of this epitope was independent of transporter of antigen presentation and proteasome function. Importantly, successful immunotherapy of MUC1-overexpressing tumors in MUC1-transgenic mice was not accompanied by damage to normal somatic MUC1-positive tissues, even when this involved the infusion of large numbers of clonal cytotoxic T lymphocyte that recognized the immunodominant MUC1 epitope. Although the risk for autoimmune pathology is limited, data indicate that immune tolerance in MUC1-positive subjects restricts the breadth of the MUC1-specific cytotoxic T lymphocyte r...Continue Reading

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Citations

Feb 8, 2005·Cancer Immunology, Immunotherapy : CII·Karl G KohlgrafMichael A Hollingsworth
Jan 18, 2005·International Immunopharmacology·Vladimir M PisarevSimon Sherman
Mar 20, 2009·Current Opinion in Immunology·Rienk Offringa
Apr 17, 2007·Journal of Peptide Science : an Official Publication of the European Peptide Society·Maciej PudelkoMikael Elofsson
Apr 12, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anne M ErcoliniElizabeth M Jaffee
Nov 3, 2004·Cancer Research·Lynn M HerbertDiana M Lopez

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