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Identification of HLA-A2-restricted CTL epitopes of a novel tumour-associated antigen, KIF20A, overexpressed in pancreatic cancer.
Imai, K; Hirata, S; Irie, A; Senju, S; Ikuta, Y; Yokomine, K; Harao, M; Inoue, M; Tomita, Y; Tsunoda, T; Nakagawa, H; Nakamura, Y; Baba, H; Nishimura, Y.
Afiliación
  • Imai K; Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Br J Cancer ; 104(2): 300-7, 2011 Jan 18.
Article en En | MEDLINE | ID: mdl-21179034
BACKGROUND: Identification of tumour-associated antigens (TAAs) that induce cytotoxic T lymphocytes (CTLs) specific to cancer cells is critical for the development of anticancer immunotherapy. In this study, we aimed at identifying a novel TAA of pancreatic cancer for immunotherapy. METHODS: On the basis of the genome-wide cDNA microarray analysis, we focused on KIF20A (also known as RAB6KIFL/MKlp2) as a candidate TAA in pancreatic cancer cells. The HLA-A2 (A*02:01)-restricted CTL epitopes of KIF20A were identified using HLA-A2 transgenic mice (Tgm) and the peptides were examined to check whether they could generate human CTLs exhibiting cytotoxic responses against KIF20A(+), HLA-A2(+) tumour cells in vitro. RESULTS: KIF20A was overexpressed in pancreatic cancer and in some other malignancies, but not in their non-cancerous counterparts and many normal adult tissues. We found that KIF20A-2 (p12-20, LLSDDDVVV), KIF20A-8 (p809-817, CIAEQYHTV), and KIF20A-28 (p284-293, AQPDTAPLPV) peptides could induce HLA-A2-restricted CTLs in HLA-A2 Tgm without causing autoimmunity. Peptide-reactive human CTLs were generated from peripheral blood mononuclear cells of HLA-A2(+) healthy donors by in vitro stimulation with the three peptides, and those CTLs successfully exhibited cytotoxic responses to cancer cells expressing both KIF20A and HLA-A2. CONCLUSION: KIF20A is a novel promising candidate for anticancer immunotherapeutic target for pancreatic cancers.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Linfocitos T Citotóxicos / Antígeno HLA-A2 / Cinesinas / Epítopos Tipo de estudio: Diagnostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Br J Cancer Año: 2011 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Linfocitos T Citotóxicos / Antígeno HLA-A2 / Cinesinas / Epítopos Tipo de estudio: Diagnostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Br J Cancer Año: 2011 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido