Assessment of immunological biomarkers in patients with advanced cancer treated by personalized peptide vaccination

Noguchi, Masanori; Mizutani, Takashi; Komatsu, Nobukazu; Suekane, Shigetaka; Moriya, Fukuko; Matsuoka, Kei; Yutani, Shigeru; Shichijo, Shigeki; Yamada, Akira; Toh, Uhi; Kawano, Keiichi; Azuma, Kouichi; Uemura, Hirotsugu; Okuno, Kiyotaka; Matsumoto, Kazumasa; Yanagimoto, Hiroaki; Yamanaka, Ryuya; Oka, M.; Todo, Satoru; Sasada, Tetsuro; Itoh, Kyogo

doi:10.4161/cbt.10.12.13448

Cited by 48 publications

(74 citation statements)

References 40 publications

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“…One of the speculated reasons why PBMC from patients with lymphocytopenia could not induce a good immune response in our study is that the release of inhibitory immunological cytokines such as transforming growth factor β or IL-10 from pancreatic adenocarcinoma tissue decreases lymphocyte counts and impairs the function of lymphocytes both systemically and in the microenvironment [44]. It was also reported that lymphocyte counts and CTL responses were prognostic markers in advanced cancer cases receiving peptide vaccine therapy [45,46]. Our results showing a correlation between the T-cell response and outcomes in pancreatic adenocarcinoma patients corresponded to these previous findings, which indicates that restricting the objective to those with an adequate lymphocyte subset could lead to a clinical trial with favorable outcomes.…”

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confidence: 94%

P53, hTERT, WT-1, and VEGFR2 are the most suitable targets for cancer vaccine therapy in HLA-A24 positive pancreatic adenocarcinoma

Terashima

Mizukoshi

Arai

et al. 2014

Cancer Immunol Immunother

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Cancer vaccine therapy is one of the most attractive therapies as a new treatment procedure for pancreatic adenocarcinoma. Recent technical advances have enabled the identification of cytotoxic T lymphocyte (CTL) epitopes in various tumor-associated antigens (TAAs). However, little is known about which TAA and its epitope are the most immunogenic and useful for a cancer vaccine for pancreatic adenocarcinoma. We

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mentioning

confidence: 94%

P53, hTERT, WT-1, and VEGFR2 are the most suitable targets for cancer vaccine therapy in HLA-A24 positive pancreatic adenocarcinoma

Terashima

Mizukoshi

Arai

et al. 2014

Cancer Immunol Immunother

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“…We have developed a novel regimen of personalized peptide vaccination (PPV), in which vaccine antigens are selected from a pool of 31 different peptide candidates based on the pre-existing immunoglobulin G (IgG) responses specific to each peptide before vaccination [13-17]. Most of the peptides employed for PPV, except for those derived from prostate-related antigens, are known to be commonly expressed in various types of advanced cancers.…”

Section: Introductionmentioning

confidence: 99%

“…Most of the peptides employed for PPV, except for those derived from prostate-related antigens, are known to be commonly expressed in various types of advanced cancers. Our previous clinical trials of PPV for patients with advanced cancers demonstrated the safety and feasibility of this new approach [13-17]. Here we conducted a phase II study of PPV for metastatic recurrent breast cancer to investigate the feasibility of PPV for mrTNBC.…”

Section: Introductionmentioning

confidence: 99%

Feasibility study of personalized peptide vaccination for metastatic recurrent triple-negative breast cancer patients

et al. 2014

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IntroductionSince treatment modalities for metastatic recurrent triple-negative breast cancer (mrTNBC) are limited, a novel treatment approach including immunotherapy is required. We have developed a novel regimen of personalized peptide vaccination (PPV), in which vaccine antigens are individually selected from a pool of different peptide candidates based on the pre-existing host immunity. Herein we conducted a phase II study of PPV for metastatic recurrent breast cancer patients to investigate the feasibility of PPV for mrTNBC.MethodsSeventy-nine patients with metastatic recurrent breast cancer who had metastases and had failed standard chemotherapy and/or hormonal therapy were enrolled. They were subgrouped as the mrTNBC group (n = 18), the luminal/human epidermal growth factor receptor 2 (HER2)-negative group (n = 41) and the HER2-positive group (n = 18), while the remaining two patients had not been investigated. A maximum of four human leukocyte antigen (HLA)-matched peptides showing higher peptide-specific immunoglobulin G (IgG) responses in pre-vaccination plasma were selected from 31 pooled peptide candidates applicable for the four HLA-IA phenotypes (HLA-A2, -A24, or -A26 types, or HLA-A3 supertypes), and were subcutaneously administered weekly for 6 weeks and bi-weekly thereafter. Measurement of peptide-specific cytotoxic T lymphocyte (CTL) and IgG responses along with other laboratory analyses were conducted before and after vaccination.ResultsNo severe adverse events associated with PPV were observed in any of the enrolled patients. Boosting of CTL and/or IgG responses was observed in most of the patients after vaccination, irrespective of the breast cancer subtypes. There were three complete response cases (1 mrTNBC and 2 luminal/HER2-negative types) and six partial response cases (1 mrTNBC and 5 luminal/HER2-negative types). The median progression-free survival time and median overall survival time of mrTNBC patients were 7.5 and 11.1 months, while those of luminal/HER2-negative patients were 12.2 and 26.5 months, and those of HER2-positive patients were 4.5 and 14.9 months, respectively.ConclusionsPPV could be feasible for mrTNBC patients because of the safety, immune responses, and possible clinical benefits.Clinical Trial Registration NumberUMIN000001844 (Registration Date: April 5, 2009)

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“…This method has been reported to allow simple, quick, and highly reproducible high-throughput screening and monitoring of IgG responses specific to a large number (~100) of peptide antigens with a tiny amount (~10 μl) of plasma [75,81].…”

Section: Rationale Of Ppvmentioning

confidence: 99%

“…Multiple (two to four) antigens are selected and administered to increase the likelihood of the vaccinated antigens matching those expressed by the tumor cells [68,69]. A series of early phase (phase I and/or phase II) clinical trials of PPV that were conducted for patients with various types of advanced cancers, including CRC, have shown the feasibility of this new approach [69][70][71][72][73][74][75][76][77][78][79][80]. For example, we have recently demonstrated that the patients treated with PPV showed a significantly longer overall survival (OS) than those with standard care and treatment in randomized phase II studies for bladder cancer and prostate cancer [72,73].…”

Section: Rationale Of Ppvmentioning

confidence: 99%

Personalized immunotherapy in colorectal cancer

Ohtake

Wada

Yada

et al. 2016

Expert Review of Precision Medicine and Drug Development

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The fields of cancer immunology and immunotherapy have made dramatic progress in the past 20 years. Various approaches to cancer immunotherapies, including cancer vaccines using peptides, proteins, DNA, and dendritic cells, have been developed to activate antigen-specific immune cells and their efficacy has been clinically examined. Herein, we summarize previously performed clinical trials of various immunotherapies against colorectal cancer (CRC), including our own novel immunotherapeutic approach, the "personalized peptide vaccine", in which human leukocyte antigen (HLA)-matched vaccine peptides are selected based on pre-existing host immunity before vaccination. In the near future, neoepitopes identified through massive DNA sequencing of the genetic alterations in tumor cells, combined with robust T cell epitope predictions in each patient might be targeted as a personalized immunotherapy for CRC. ARTICLE HISTORY

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Assessment of immunological biomarkers in patients with advanced cancer treated by personalized peptide vaccination

Cited by 48 publications

References 40 publications

P53, hTERT, WT-1, and VEGFR2 are the most suitable targets for cancer vaccine therapy in HLA-A24 positive pancreatic adenocarcinoma

P53, hTERT, WT-1, and VEGFR2 are the most suitable targets for cancer vaccine therapy in HLA-A24 positive pancreatic adenocarcinoma

Feasibility study of personalized peptide vaccination for metastatic recurrent triple-negative breast cancer patients

Personalized immunotherapy in colorectal cancer

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