Nucleophosmin is recognized by a cytotoxic T cell line derived from a rectal carcinoma patient.
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.
Swoboda
Rolf K
RK
The Wistar Institute, 3601 Spruce Street, Philadelphia PA 19104, USA.
Somasundaram
Rajasekharan
R
Caputo
Laura
L
Berencsi
Klara
K
von Franzke
Paul
P
Taylor
Douglas D
DD
Marincola
Francesco M
FM
Meropol
Neal J
NJ
Sigurdson
Elin
E
Miller
Eric
E
Herlyn
Dorothee
D
D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology; D005260:Female; D015788:HLA-A1 Antigen / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology / Q000473:pathology; D009687:Nuclear Proteins / Q000276:immunology*; D000090243:Nucleophosmin; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology*; D012004:Rectal Neoplasms / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; D015788:HLA-A1 Antigen; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D010446:Peptide Fragments; D000090243:Nucleophosmin