Identification of HLA-A24-Restricted Novel T Cell Epitope Peptides Derived from P-Cadherin and Kinesin Family Member 20A

Osawa, Ryuji; Tsunoda, Takuya; Yoshimura, Satoshi; Watanabe, Tsutomu; Miyazawa, Motoki; Tani, Masaji; Takeda, Kazuyoshi; Nakagawa, Hidewaki; Nakamura, Yusuke; Yamaue, Hiroki

doi:10.1155/2012/848042

Cited by 22 publications

(22 citation statements)

References 26 publications

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“…Knockdown of KIF20A in pancreatic cancer cells can significantly inhibit cell proliferation,17,18 indicating the significance of its overexpression in human cancers. Studies have also reported that several peptides derived from KIF20A can be helpful to activate the immune system and kill the cancer cells which endogenously express KIF20A antigen 16,19,20. Several groups are carrying out the phase I/II clinical trials for immunotherapy using these KIF20-derived peptides 21.…”

Section: Introductionmentioning

confidence: 99%

Positive expression of KIF20A indicates poor prognosis of glioma patients

Duan

Huang

2016

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Glioma patients have a poor overall survival; however, patients can show distinct clinical outcomes due to the high heterogeneity of the tumor, which may be indicated by certain clinicobiological parameters. Kinesin family member 20A (KIF20A), which participates in cytokinesis and intracellular transportation, has been recently reported to be upregulated in pancreatic cancer, breast cancer, and bladder cancer. In the current study, we investigated the expression of KIF20A in gliomas and its significance in predicting the prognosis after surgery. We found that KIF20A positive expression in glioma tissues correlated significantly with Ki67 protein expression and advanced World Health Organization grade. Univariate and multivariate analysis revealed that KIF20A can act as an independent prognostic factor for predicting the overall survival of glioma patients. Moreover, we demonstrated that KIF20A can positively regulate the expression of Ki67 in glioma cell lines. Correspondingly, overexpression of KIF20A can promote cell proliferation and invasion, whereas knockdown of KIF20A can inhibit cell viability and invasion capacity. In vitro study also showed that under the treatment of plumbagin, an anticancer drug, KIF20A expression decreased in a dose-dependent manner. In addition, the overexpression of KIF20A can also increase the drug resistance toward plumbagin, which provided the possibility that KIF20A may contribute to the chemotherapy resistance of gliomas.

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Section: Introductionmentioning

confidence: 99%

Positive expression of KIF20A indicates poor prognosis of glioma patients

Duan

Huang

2016

OTT

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“…KIF20A has been reported to be a promising immunotherapeutic target for cancers. Studies have reported that 2 short peptides (SP) derived from KIF20A, KIF20A-A2 , and KIF20A-A24 66-75 stimulated CTLs, which kill cancer cells endogenously expressing KIF20A antigen and that KIF20A-specific CTLs were present in peripheral blood mononuclear cells (PBMC) obtained from patients with pancreatic cancer (1,4). Phase I/II clinical trials of cancer immunotherapy for lung cancer, pancreatic cancer, and cholangiocellular carcinoma using KIF20A-derived SP are underway.…”

Section: Introductionmentioning

confidence: 99%

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

Tomita

Yuno

Tsukamoto

et al. 2013

Clinical Cancer Research

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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 (T H 1) 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 Ã 02:01) or HLA-A24 (A Ã 24:02) to select candidate promiscuous T H 1-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 T H 1-cell response to KIF20A-LPs in HNMT patients receiving immunotherapy with TAA-derived CTL-epitope peptides was analyzed using IFN-g enzyme-linked immunospot assays. Results: We identified promiscuous KIF20A-LPs bearing naturally processed epitopes recognized by CD4 þ 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 T H 1 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 T H 1 cell responses in HNMT patients and underline the possible utility of KIF20A-LPs for propagation of T H 1 cells and CTLs.

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“…The targeting oncogenic antigens can avoid the immune escape of cancer cells by lacking these proteins [22,23] . Epitope peptides of several oncoantigens such as kinesin family member 20A (KIF20A), lymphocyte antigen 6 complex locus K (LY6K), DEP domain-containing 1 (DEPDC1), forkhead box M1 (FOXM1), cell division cycleassociated 1 (CDCA1), cadherin 3/P-cadherin (CDH3), insulin-like growth factor-II mRNAbinding protein 3 (IMP-3) and others have been developed for clinical trials [24][25][26][27][28][29][30][31][32][33] .…”

Section: Oncoantigensmentioning

confidence: 99%

Cancer vaccine therapy based on peptides

Katsuda

Yamaue

2017

Trends Immunother

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Following numerous unequivocal clinical failures, immunotherapy has become an attractive therapeutic modality. Peptide vaccines are cost-effective compared to other vaccine approaches, and effective epitopes eliciting strong immune response can be selected experimentally in silico and ex vivo. However, the clinical benefits of cancer peptides vaccine have been disappointing in most studies; therefore, we need to prove the clinical beneficial effects for cancer treatment following induction of more powerful cytotoxic T lymphocytes (CTLs). First, the choice of ideal target antigen is essential. Epitopes derived from tumor-associated antigens (TAAs), oncoantigens, vascular endothelial cells and neoantigens are then developed. In particular, wholeexome sequencing enables us to identify the epitopes of neoantigens. The choice of therapeutic objectives is also important and peptide vaccines might be better to be developed as preventative vaccines. Dendritic cells (DCs) vaccine pulsed with peptides is an approach to induce powerful CTLs and might overcome several disadvantages of peptide vaccines as monotherapy. Targeting vaccine therapy against DC subsets in vivo is under development.

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Identification of HLA-A24-Restricted Novel T Cell Epitope Peptides Derived from P-Cadherin and Kinesin Family Member 20A

Cited by 22 publications

References 26 publications

Positive expression of KIF20A indicates poor prognosis of glioma patients

Positive expression of KIF20A indicates poor prognosis of glioma patients

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

Cancer vaccine therapy based on peptides

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