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

• Published in: Clinical cancer research 2013-08, Vol.19 (16), p.4508-4520
• Main Authors: TOMITA, Yusuke, YUNO, Akira, JONO, Hirofumi, YOSHIDA, Koji, TSUNODA, Takuya, KOHROGI, Hirotsugu, YOSHITAKE, Yoshihiro, NAKAMURA, Yusuke, SHINOHARA, Masanori, NISHIMURA, Yasuharu, TSUKAMOTO, Hirotake, SENJU, Satoru, KURODA, Yasuhiro, HIRAYAMA, Masatoshi, IRIE, Atsushi, KAWAHARA, Kenta, YATSUDA, Junji, HAMADA, Akinobu
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Animals; Antigen Presentation - immunology; Antigens, Neoplasm - immunology; Antineoplastic agents; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Cell Line; Dendritic Cells; Epitopes, T-Lymphocyte - immunology; Female; Head and Neck Neoplasms - immunology; Head and Neck Neoplasms - pathology; Head and Neck Neoplasms - therapy; Histocompatibility Antigens Class II - immunology; Histocompatibility Antigens Class II - metabolism; Humans; Immunotherapy; Kinesin - chemistry; Kinesin - immunology; Kinesin - metabolism; Male; Medical sciences; Mice; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasms - immunology; Neoplasms - metabolism; Neoplasms - pathology; Neoplasms - therapy; Peptides - immunology; Peptides - metabolism; Pharmacology. Drug treatments; Protein Binding; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Helper-Inducer - immunology; Tumors
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-13-0197

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. 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. 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. 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.