5-Fluorouracil (5-FU) is a pyrimidine antimetabolite active against colorectal carcinoma and other malignancies of the digestive tract. Over-expression or mutation of thymidylate synthase (TS), the target enzyme of the 5-FU metabolite, 5-fluorodeoxyuridine monophosphate, is strictly correlated with cancer cell resistance to 5-FU. On this basis we investigated whether TS is a potential target for active specific immunotherapy of human colon carcinoma, which acquires resistance to 5-FU. Three TS-derived epitope peptides which fit defined amino acid consensus motifs for HLA-A2.1 binding were synthesized and investigated for their ability to induce human TS-specific cytotoxic T cell (CTL) responses in vitro. CTL lines specific for each peptide were established by stimulating peripheral blood mononuclear cells (PBMC) from an HLA-A2.1+ healthy donor with autologous dendritic cells loaded with TS peptide. Specific CTL lines showed HLA-A2.1-restricted cytotoxicity in vitro to HLA-A2.1+ target cells pulsed with the specific TS peptide and to HLA-class I matching colon carcinoma target cells over-expressing TS enzyme after exposure to 5-FU. Recognition by CTL lines suggests that these TS peptides may be potential candidates for use in a peptide-based vaccine against 5-FU resistant colon carcinoma.

Correale, P., Sabatino, M., Cusi, M., Micheli, L., Nencini, C., Pozzessere, D., et al. (2001). In vitro generation of cytotoxic T lymphocytes against HLA-A2.1-restricted peptides derived from human thymidylate synthase. JOURNAL OF CHEMOTHERAPY, 13(5), 519-526.

In vitro generation of cytotoxic T lymphocytes against HLA-A2.1-restricted peptides derived from human thymidylate synthase

AQUINO, ANGELO;DE VECCHIS, LIANA;TURRIZIANI, MARIO;PRETE, SALVATORE;
2001-10-01

Abstract

5-Fluorouracil (5-FU) is a pyrimidine antimetabolite active against colorectal carcinoma and other malignancies of the digestive tract. Over-expression or mutation of thymidylate synthase (TS), the target enzyme of the 5-FU metabolite, 5-fluorodeoxyuridine monophosphate, is strictly correlated with cancer cell resistance to 5-FU. On this basis we investigated whether TS is a potential target for active specific immunotherapy of human colon carcinoma, which acquires resistance to 5-FU. Three TS-derived epitope peptides which fit defined amino acid consensus motifs for HLA-A2.1 binding were synthesized and investigated for their ability to induce human TS-specific cytotoxic T cell (CTL) responses in vitro. CTL lines specific for each peptide were established by stimulating peripheral blood mononuclear cells (PBMC) from an HLA-A2.1+ healthy donor with autologous dendritic cells loaded with TS peptide. Specific CTL lines showed HLA-A2.1-restricted cytotoxicity in vitro to HLA-A2.1+ target cells pulsed with the specific TS peptide and to HLA-class I matching colon carcinoma target cells over-expressing TS enzyme after exposure to 5-FU. Recognition by CTL lines suggests that these TS peptides may be potential candidates for use in a peptide-based vaccine against 5-FU resistant colon carcinoma.
ott-2001
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/14 - FARMACOLOGIA
Settore MED/06 - ONCOLOGIA MEDICA
English
Con Impact Factor ISI
Cancer Vaccines; Antimetabolites, Antineoplastic; Humans; Drug Resistance, Neoplasm; Carcinoma; HLA-A2 Antigen; Epitopes, T-Lymphocyte; Tumor Cells, Cultured; Thymidylate Synthase; Fluorouracil; T-Lymphocytes, Cytotoxic; Flow Cytometry; Peptides; Colonic Neoplasms; Cell Line
Correale, P., Sabatino, M., Cusi, M., Micheli, L., Nencini, C., Pozzessere, D., et al. (2001). In vitro generation of cytotoxic T lymphocytes against HLA-A2.1-restricted peptides derived from human thymidylate synthase. JOURNAL OF CHEMOTHERAPY, 13(5), 519-526.
Correale, P; Sabatino, M; Cusi, M; Micheli, L; Nencini, C; Pozzessere, D; Petrioli, R; Aquino, A; DE VECCHIS, L; Turriziani, M; Prete, S; Sanguedolce, R; Rausa, L; Giorgi, G; Francini, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/51750
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