Identification of HLA-A*0201/-A*2402-restricted CTL epitopepeptides derived from a novel cancer/testis antigen, MCAK, and induction of a specific antitumor immune response

Megumi Kawamoto, Fumiaki Tanaka, Koshi Mimori, Hiroshi Inoue, Yukio Kamohara, Masaki Mori

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Cancer immunotherapy is a potential therapeutic strategy, in addition to surgical treatment, radiotherapy, and chemotherapy. Cancer-specific immunotherapy, such as the MAGE peptide vaccine, has been utilized clinically. However, there are inherent limits to the effectiveness of vaccinotherapy using a single antigen because of the expression frequency of cancer-specific antigens on tumor cells. Thus, identification of a new cancer-specific antigen is needed. In this study, we examined the possibility of using cancer-specific immunotherapy based upon mitotic centromere-associated kinesin (MCAK) which was previously identified as a novel cancer/testis antigen. To evaluate the feasibility of developing cancer immunotherapy using MCAK peptides, we studied HLA-A*0201 and *2402 as targets for CTLs in the context of HLA class I molecules. By using a peptide with a sequence of AINPELLQL (amino acid positions 63-71 in MCAK, HLA-A*0201) and FFEIYNGKL (amino acid positions 401-409 in MCAK, HLA-A*2402), CTL responses could be induced from unseparated PBMCs by stimulation of freshly isolated, peptide-pulsed PBMCs as antigen-presenting cells (APCs) and also by using interleukin-7 and keyhole limpet hemocyanin in primary culture. The induced CTLs could lyse HLA-A-*0201/*2402 colon and gastric cancer cells expressing MCAK, as well as the peptide-pulsed target cells, in an HLA class l, and CD8 restricted manner. The identification of the MCAK/HLA-A*0201 and *2402 peptides suggests the possibility of designing peptide-based immunotherapeutic approaches that might prove effective in treating patients with MCAK-positive cancer.

Original languageEnglish
Pages (from-to)469-476
Number of pages8
JournalOncology reports
Volume25
Issue number2
DOIs
Publication statusPublished - Feb 1 2011

Fingerprint

Kinesin
Centromere
Testicular Neoplasms
Antigens
Immunotherapy
Peptides
Neoplasms
Interleukin-7
Subunit Vaccines
HLA-A Antigens
Neoplasm Antigens
Antigen-Presenting Cells
HLA-A*02:01 antigen
Colonic Neoplasms
Stomach Neoplasms
Amino Acid Sequence
Radiotherapy
Amino Acids
Drug Therapy
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Identification of HLA-A*0201/-A*2402-restricted CTL epitopepeptides derived from a novel cancer/testis antigen, MCAK, and induction of a specific antitumor immune response. / Kawamoto, Megumi; Tanaka, Fumiaki; Mimori, Koshi; Inoue, Hiroshi; Kamohara, Yukio; Mori, Masaki.

In: Oncology reports, Vol. 25, No. 2, 01.02.2011, p. 469-476.

Research output: Contribution to journalArticle

@article{901189644e6d4087a6606103809df7c4,
title = "Identification of HLA-A*0201/-A*2402-restricted CTL epitopepeptides derived from a novel cancer/testis antigen, MCAK, and induction of a specific antitumor immune response",
abstract = "Cancer immunotherapy is a potential therapeutic strategy, in addition to surgical treatment, radiotherapy, and chemotherapy. Cancer-specific immunotherapy, such as the MAGE peptide vaccine, has been utilized clinically. However, there are inherent limits to the effectiveness of vaccinotherapy using a single antigen because of the expression frequency of cancer-specific antigens on tumor cells. Thus, identification of a new cancer-specific antigen is needed. In this study, we examined the possibility of using cancer-specific immunotherapy based upon mitotic centromere-associated kinesin (MCAK) which was previously identified as a novel cancer/testis antigen. To evaluate the feasibility of developing cancer immunotherapy using MCAK peptides, we studied HLA-A*0201 and *2402 as targets for CTLs in the context of HLA class I molecules. By using a peptide with a sequence of AINPELLQL (amino acid positions 63-71 in MCAK, HLA-A*0201) and FFEIYNGKL (amino acid positions 401-409 in MCAK, HLA-A*2402), CTL responses could be induced from unseparated PBMCs by stimulation of freshly isolated, peptide-pulsed PBMCs as antigen-presenting cells (APCs) and also by using interleukin-7 and keyhole limpet hemocyanin in primary culture. The induced CTLs could lyse HLA-A-*0201/*2402 colon and gastric cancer cells expressing MCAK, as well as the peptide-pulsed target cells, in an HLA class l, and CD8 restricted manner. The identification of the MCAK/HLA-A*0201 and *2402 peptides suggests the possibility of designing peptide-based immunotherapeutic approaches that might prove effective in treating patients with MCAK-positive cancer.",
author = "Megumi Kawamoto and Fumiaki Tanaka and Koshi Mimori and Hiroshi Inoue and Yukio Kamohara and Masaki Mori",
year = "2011",
month = "2",
day = "1",
doi = "10.3892/or.2010.1101",
language = "English",
volume = "25",
pages = "469--476",
journal = "Oncology Reports",
issn = "1021-335X",
publisher = "Spandidos Publications",
number = "2",

}

TY - JOUR

T1 - Identification of HLA-A*0201/-A*2402-restricted CTL epitopepeptides derived from a novel cancer/testis antigen, MCAK, and induction of a specific antitumor immune response

AU - Kawamoto, Megumi

AU - Tanaka, Fumiaki

AU - Mimori, Koshi

AU - Inoue, Hiroshi

AU - Kamohara, Yukio

AU - Mori, Masaki

PY - 2011/2/1

Y1 - 2011/2/1

N2 - Cancer immunotherapy is a potential therapeutic strategy, in addition to surgical treatment, radiotherapy, and chemotherapy. Cancer-specific immunotherapy, such as the MAGE peptide vaccine, has been utilized clinically. However, there are inherent limits to the effectiveness of vaccinotherapy using a single antigen because of the expression frequency of cancer-specific antigens on tumor cells. Thus, identification of a new cancer-specific antigen is needed. In this study, we examined the possibility of using cancer-specific immunotherapy based upon mitotic centromere-associated kinesin (MCAK) which was previously identified as a novel cancer/testis antigen. To evaluate the feasibility of developing cancer immunotherapy using MCAK peptides, we studied HLA-A*0201 and *2402 as targets for CTLs in the context of HLA class I molecules. By using a peptide with a sequence of AINPELLQL (amino acid positions 63-71 in MCAK, HLA-A*0201) and FFEIYNGKL (amino acid positions 401-409 in MCAK, HLA-A*2402), CTL responses could be induced from unseparated PBMCs by stimulation of freshly isolated, peptide-pulsed PBMCs as antigen-presenting cells (APCs) and also by using interleukin-7 and keyhole limpet hemocyanin in primary culture. The induced CTLs could lyse HLA-A-*0201/*2402 colon and gastric cancer cells expressing MCAK, as well as the peptide-pulsed target cells, in an HLA class l, and CD8 restricted manner. The identification of the MCAK/HLA-A*0201 and *2402 peptides suggests the possibility of designing peptide-based immunotherapeutic approaches that might prove effective in treating patients with MCAK-positive cancer.

AB - Cancer immunotherapy is a potential therapeutic strategy, in addition to surgical treatment, radiotherapy, and chemotherapy. Cancer-specific immunotherapy, such as the MAGE peptide vaccine, has been utilized clinically. However, there are inherent limits to the effectiveness of vaccinotherapy using a single antigen because of the expression frequency of cancer-specific antigens on tumor cells. Thus, identification of a new cancer-specific antigen is needed. In this study, we examined the possibility of using cancer-specific immunotherapy based upon mitotic centromere-associated kinesin (MCAK) which was previously identified as a novel cancer/testis antigen. To evaluate the feasibility of developing cancer immunotherapy using MCAK peptides, we studied HLA-A*0201 and *2402 as targets for CTLs in the context of HLA class I molecules. By using a peptide with a sequence of AINPELLQL (amino acid positions 63-71 in MCAK, HLA-A*0201) and FFEIYNGKL (amino acid positions 401-409 in MCAK, HLA-A*2402), CTL responses could be induced from unseparated PBMCs by stimulation of freshly isolated, peptide-pulsed PBMCs as antigen-presenting cells (APCs) and also by using interleukin-7 and keyhole limpet hemocyanin in primary culture. The induced CTLs could lyse HLA-A-*0201/*2402 colon and gastric cancer cells expressing MCAK, as well as the peptide-pulsed target cells, in an HLA class l, and CD8 restricted manner. The identification of the MCAK/HLA-A*0201 and *2402 peptides suggests the possibility of designing peptide-based immunotherapeutic approaches that might prove effective in treating patients with MCAK-positive cancer.

UR - http://www.scopus.com/inward/record.url?scp=78651374344&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78651374344&partnerID=8YFLogxK

U2 - 10.3892/or.2010.1101

DO - 10.3892/or.2010.1101

M3 - Article

C2 - 21165574

AN - SCOPUS:78651374344

VL - 25

SP - 469

EP - 476

JO - Oncology Reports

JF - Oncology Reports

SN - 1021-335X

IS - 2

ER -