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Swoboda RK , Somasundaram R , Caputo L , Berencsi K , von Franzke P , Taylor DD , Marincola FM , Meropol NJ , Sigurdson E , Miller E , Herlyn D
Nucleophosmin is recognized by a cytotoxic T cell line derived from a rectal carcinoma patient
International Journal of Cancer. 2010 Sep;127(5) :1124-1130
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Abstract
Immunotherapy of colorectal carcinoma (CRC) has great promise as the presence of T lymphocytes in CRC tissues in situ is correlated with reduced recurrence and increased survival. Thus, identification of the antigens recognized by T cells of CRC patients may permit development of vaccines with potential benefit for these patients. Using expression cloning, we identified the antigen, nucleophosmin (Npm), recognized by an HLA-A1 restricted cytotoxic T lymphocyte (CTL) line derived from the peripheral blood mononuclear cells (PBMC) of a rectal cancer patient. A decamer peptide derived from the Npm sequence sensitized peptide-pulsed HLA-A1 positive cells to lysis by the CTL line. The peptide also induced proliferative and cytotoxic T lymphocytes in the PBMC of 4 of 6 CRC patients, which lysed HLA-A1 positive peptide-pulsed target cells and CRC cells endogenously expressing Npm. Overexpression of Npm by tumors of various histological types, recognition of the antigen by T cells derived from different CRC patients and association of the antigen with poor prognostic outcome make it a promising target for immunotherapeutic intervention in cancer patients.
Notes
Swoboda, Rolf K. Somasundaram, Rajasekharan Caputo, Laura Berencsi, Klara von Franzke, Paul Taylor, Douglas D. Marincola, Francesco M. Meropol, Neal J. Sigurdson, Elin Miller, Eric Herlyn, Dorothee John wiley & sons inc Hoboken 635kk