Identification of an HLA-A2-Restricted Epitope Peptide Derived from Hypoxia-Inducible Protein 2 (HIG2)

Yoshimura, Satoshi; Tsunoda, Takuya; Osawa, Ryuji; Harada, Makiko; Watanabe, Tsutomu; Hikichi, Tetsuro; Katsuda, Masahiro; Miyazawa, Motoki; Tani, Masaji; Itō, Makoto; Takeda, Kazuyoshi; Katagiri, Toyomasa; Nakamura, Yusuke; Yamaue, Hiroki

doi:10.1371/journal.pone.0085267

Cited by 11 publications

(16 citation statements)

References 43 publications

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“…These results strongly indicated that vaccination with oncoantigen‐derived peptides can induce specific CTL potently cytotoxic to HLA‐A matched cancer cells expressing oncoantigen. Thus, we identified several oncoantigen‐derived epitope peptides by measuring the induction of activation of specific CTL . We have also tested these peptides in clinical investigations against several urological cancers.…”

Section: Development Of Peptide Vaccine Therapy Using Oncoantigenmentioning

confidence: 99%

Present status and future perspective of peptide‐based vaccine therapy for urological cancer

et al. 2018

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Use of peptide‐based vaccines as therapeutics aims to elicit immune responses through antigenic epitopes derived from tumor antigens. Peptide‐based vaccines are easily synthesized and lack significant side‐effects when given in vivo. Peptide‐based vaccine therapy against several cancers including urological cancers has made progress for several decades, but there is no worldwide approved peptide vaccine. Peptide vaccines were also shown to induce a high frequency of immune response in patients accompanied by clinical efficacy. These data are discussed in light of the recent progression of immunotherapy caused by the addition of immune checkpoint inhibitors thus providing a general picture of the potential therapeutic efficacy of peptide‐based vaccines and their combination with other biological agents. In this review, we discuss the mechanism of the antitumor effect of peptide‐based vaccine therapy, development of our peptide vaccine, recent clinical trials using peptide vaccines for urological cancers, and perspectives of peptide‐based vaccine therapy.

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Section: Development Of Peptide Vaccine Therapy Using Oncoantigenmentioning

confidence: 99%

Present status and future perspective of peptide‐based vaccine therapy for urological cancer

et al. 2018

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“…As one of the approaches to develop a novel treatment option, we previously developed the HLA-A*0201/0206-restricted HIG2-derived epitope peptide, HIG2-9-4 [8]. In the present study, we conducted a phase I clinical trial using the HIG2-9-4 peptide for patients with advanced RCC.…”

Section: Discussionmentioning

confidence: 99%

“…HIG2-derived 9- and 10-mer peptides that have high binding affinity to HLA-A:*02:01 were identified as candidates by using the binding prediction software, BioInformatics and molecular analysis section (BIMAS), and the homologous sequences were screened by using the homology search program, basic local alignment search tool (BLAST), as previously reported [8]. The selected high-affinity peptide, HIG2-9-4 peptide (VLNLYLLGV), was manufactured as good manufacturing practice (GMP) grade at a purity of >95 % for the clinical trial by the American Peptide Company Inc. (Sunnyvale, CA).…”

Section: Methodsmentioning

confidence: 99%

“…Because HIG2 expression was specific to RCC and had an expression that was hardly detectable in normal organs, we considered HIG2 to be a good candidate for the development of molecular-targeted therapies against RCC. As one of the approaches to develop anti-HIG2 drugs, we screened and identified a human leukocyte antigen (HLA)-A*0201/0206-restricted epitope peptide, named HIG2-9-4 peptide that could have a high antigenic activity to induce CTLs [8]. So, far, several peptide epitopes derived from cancer-testis antigens or oncofetal proteins have been investigated in translational research targeting several types of human cancer [9–17].…”

Section: Introductionmentioning

confidence: 99%

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Effective induction of cytotoxic T cells recognizing an epitope peptide derived from hypoxia-inducible protein 2 (HIG2) in patients with metastatic renal cell carcinoma

Obara

Karashima

Takeda

et al. 2016

Cancer Immunol Immunother

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PurposeThrough genome-wide expression profile analysis, hypoxia-inducible protein 2 (HIG2) has previously been identified as an oncoprotein involved in development/progression of renal cell carcinoma (RCC). We subsequently identified a highly immunogenic HLA-A*0201/0206-restricted epitope peptide (HIG2-9-4) corresponding to a part of HIG2 and applied it as a therapeutic vaccine. We conducted a phase I clinical trial using the HIG2-9-4 peptide for patients with advanced RCC.Materials and MethodsNine patients having HLA-A*0201 or HLA-A*0206 with metastatic or unresectable RCC after failure of the cytokine and/or tyrosine kinase inhibitor therapies were enrolled in this study. The patients received subcutaneous administration of the peptide as an emulsion form with Montanide ISA-51 VG once a week in a dose-escalation manner (doses of 0.5, 1.0, or 3.0 mg/body, 3 patients for each dose). The primary endpoint was safety, and the secondary endpoints were immunological and clinical responses.ResultsVaccinations with HIG2-9-4 peptide could be well tolerated without any serious systemic adverse events. Peptide-specific cytotoxic T lymphocyte (CTL) responses were detected in eight of the nine patients. Doses of 1.0 or 3.0 mg/body seemed to induce a CTL response better than did a dose of 0.5 mg/body, although the number of patients was too small to draw a firm conclusion. The disease control rate (stable disease for ≥4 months) was 77.8 %, and the median progression-free survival time was 10.3 months.ConclusionsHIG2-9-4 peptide vaccine treatment was tolerable and effectively induced peptide-specific CTLs in RCC patients. This novel peptide vaccine therapy for RCC is promising.

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“…Thus, theoretically, integrated application of six servers will improve the accuracy of in silico identification of CTL epitopes in Rv3117 and Rv3120 proteins. In fact, these online servers have been successfully used for the identification of T cell epitopes against different pathogens [24,25] and cancers [26]. Since NetCTL provides epitope prediction with 54-89% sensitivity and 94-99% specificity, we first employed NetCTL to predict CTL epitopes in Rv3117 and Rv3120 proteins at the default prediction value 0.75, which had 80% sensitivity and 97% specificity in a previous study [12].…”

Section: Proteinmentioning

confidence: 99%

In silico identification of cytotoxic T lymphocyte epitopes encoded by RD5 region of Mycobacterium tuberculosis

Zhao

Yan

Shi

et al. 2017

J Infect Dev Ctries

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Introduction: While CD8+ T cells (cytotoxic T lymphocytes, CTLs) play important roles in immunity against Mycobacterium tuberculosis, only a small number of human leukocyte differentiation antigen (HLA) class I-restricted CTL epitopes for TB have been identified. The current study evaluates CTL epitopes of Rv3117 and Rv3120 proteins, two newly found M. tuberculosis region-diffference-5 (RD5)-encoded antigens, and their population coverage. Methodology: The amino acid sequences of the two proteins were subjected to epitope analysis under HLA-A2, A3 and B7 supertype restriction using NetCTL, SYFPEITHI, BIMAS, NetCTLPan, IEDB, NetMHC and NetMHCPan prediction online servers. Results: Eight RD5-encoded CTL epitopes were identified in the two proteins and the average population coverage of these epitopes was 87.2% among populations worldwide. Conclusion: These CTL epitopes that were identified in silico and may have potential use for CD8+ T cell-mediated TB vaccine design.

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Identification of an HLA-A2-Restricted Epitope Peptide Derived from Hypoxia-Inducible Protein 2 (HIG2)

Cited by 11 publications

References 43 publications

Present status and future perspective of peptide‐based vaccine therapy for urological cancer

Present status and future perspective of peptide‐based vaccine therapy for urological cancer

Effective induction of cytotoxic T cells recognizing an epitope peptide derived from hypoxia-inducible protein 2 (HIG2) in patients with metastatic renal cell carcinoma

In silico identification of cytotoxic T lymphocyte epitopes encoded by RD5 region of Mycobacterium tuberculosis

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