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2 results on '"HLA-transgenic mouse"'

1. Identification of HLA-A2-restricted CTL epitopes of a novel tumour-associated antigen, KIF20A, overexpressed in pancreatic cancer.

Author

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., and Nishimura, Y.

Subjects
*HLA histocompatibility antigens, *ANTIBODY-dependent cell cytotoxicity, *CELL-mediated cytotoxicity, *ANTINEOPLASTIC agents, *IMMUNOTHERAPY, *LABORATORY mice, *PANCREATIC cancer, *AMINO acids, *ANIMAL experimentation, *ANTIGENS, *COMPARATIVE studies, *DNA probes, *DOCUMENTATION, *IMMUNOHISTOCHEMISTRY, *RESEARCH methodology, *MEDICAL cooperation, *MICE, *NUCLEOTIDES, *PANCREATIC tumors, *POLYMERASE chain reaction, *RESEARCH, *T cells, *WESTERN immunoblotting, *HLA-B27 antigen, *EVALUATION research, *REVERSE transcriptase polymerase chain reaction, *OLIGONUCLEOTIDE arrays
Abstract

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. [ABSTRACT FROM AUTHOR]

Published
2011
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2. Identification of HLA-A2-restricted CTL epitopes of a novel tumour-associated antigen, KIF20A, overexpressed in pancreatic cancer

Author

Yusuke Tomita, Atsushi Irie, Yusuke Nakamura, Satoru Senju, Hidewaki Nakagawa, Kazunori Yokomine, Hideo Baba, Tatsuhiko Tsunoda, Mitsuhiro Inoue, Michiko Harao, Yasuharu Nishimura, Shinya Hirata, Yoshiaki Ikuta, and K. Imai

Subjects
Cancer Research, Pancreatic disease, medicine.medical_treatment, Blotting, Western, Molecular Sequence Data, HLA-transgenic mouse, Kinesins, Biology, Epitope, Epitopes, Mice, Antigen, Pancreatic cancer, HLA-A2 Antigen, medicine, Animals, Humans, Amino Acid Sequence, DNA Primers, Oligonucleotide Array Sequence Analysis, Mice, Knockout, Base Sequence, Reverse Transcriptase Polymerase Chain Reaction, Cancer, Immunotherapy, anticancer immunotherapy, tumour-associated antigen, medicine.disease, Immunohistochemistry, KIF20A/RAB6KIFL/MKlp2, Pancreatic Neoplasms, CTL, Oncology, Immunology, Translational Therapeutics, T-Lymphocytes, Cytotoxic
Abstract

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.

Published
2010
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