Identification of promiscuous KIF20A long peptides bearing both CD4+ and CD8+ T-cell epitopes: KIF20A-specific CD4+ T-cell immunity in patients with malignant tumor.

Abstract

PURPOSE:

To identify long peptides (LP) derived from a novel tumor-associated antigen (TAA), kinesin family member 20A (KIF20A), which induce tumor-specific T-helper type 1 (TH1) cells and CTLs.

EXPERIMENTAL DESIGN:

We combined information from a recently developed computer algorithm predicting HLA class II-binding peptides with KIF20A-derived CTL-epitope sequences presented by HLA-A2 (A*02:01) or HLA-A24 (A*24:02) to select candidate promiscuous TH1-cell epitopes containing CTL epitopes. Peripheral blood mononuclear cells (PBMC) derived from healthy donors or patients with head-and-neck malignant tumor (HNMT) were used to study the immunogenicity of KIF20A-LPs, and the in vitro cross-priming potential of KIF20A-LPs bearing CTL epitopes. We used HLA-A24 transgenic mice to address whether vaccination with KIF20A-LP induces efficient cross-priming of CTLs in vivo. The TH1-cell response to KIF20A-LPs in HNMT patients receiving immunotherapy with TAA-derived CTL-epitope peptides was analyzed using IFN-γ enzyme-linked immunospot assays.

RESULTS:

We identified promiscuous KIF20A-LPs bearing naturally processed epitopes recognized by CD4(+) T cells and CTLs. KIF20A-specific CTLs were induced by vaccination with a KIF20A-LP in vivo. KIF20A expression was detected in 55% of HNMT by immunohistochemistry, and significant frequencies of KIF20A-specific TH1 cell responses were detected after short-term in vitro stimulation of PBMCs with KIF20A-LPs in 50% of HNMT patients, but not in healthy donors. Furthermore, these responses were associated with KIF20A expression in HNMT tissues.

CONCLUSIONS:

These are the first results showing the presence of KIF20A-specific TH1 cell responses in HNMT patients and underline the possible utility of KIF20A-LPs for propagation of TH1 cells and CTLs.

• Authors: Yusuke Tomita, Akira Yuno, Hirotake Tsukamoto, Satoru Senju, Yasuhiro Kuroda, Masatoshi Hirayama, Atsushi Irie, Kenta Kawahara, Junji Yatsuda, Akinobu Hamada, Hirofumi Jono, Koji Yoshida, Takuya Tsunoda, Hirotsugu Kohrogi, Yoshihiro Yoshitake, Yusuke Nakamura, Masanori Shinohara, Yasuharu Nishimura
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 19 Issue 16 Pg. 4508-20 (Aug 15 2013) ISSN: 1557-3265 [Electronic] United States
• PMID: 23714729 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2013 AACR.

Chemical References

• Antigens, Neoplasm
• Epitopes, T-Lymphocyte
• Histocompatibility Antigens Class II
• KIF20A protein, human
• Peptides
• Kinesins

Topics

• Adult
• Aged
• Aged, 80 and over
• Animals
• Antigen Presentation (immunology)
• Antigens, Neoplasm (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cell Line
• Dendritic Cells
• Epitopes, T-Lymphocyte (immunology)
• Female
• Head and Neck Neoplasms (immunology, pathology, therapy)
• Histocompatibility Antigens Class II (immunology, metabolism)
• Humans
• Immunotherapy
• Kinesins (chemistry, immunology, metabolism)
• Male
• Mice
• Middle Aged
• Neoplasms (immunology, metabolism, pathology, therapy)
• Peptides (immunology, metabolism)
• Protein Binding
• T-Lymphocytes, Cytotoxic (immunology)
• T-Lymphocytes, Helper-Inducer (immunology)