Peptide vaccines in cancer — old concept revisited

Kumai, Takumi; Kobayashi, Hiroya; Harabuchi, Yasuaki; Celis, Esteban

doi:10.1016/j.coi.2016.11.001

Cited by 98 publications

(74 citation statements)

References 69 publications

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“…Since the discovery of cancer‐related antigens in the 1990s, cancer immunotherapy has developed as a promising cancer treatment based on cancer‐specific activation of the host immune system . To date, many basic studies and clinical trials of cancer peptide vaccines and adoptive T cell therapies have been conducted for the treatment of cancer patients . However, while some trials have reported clinical efficacy, cancer vaccine therapies are not yet a standard therapy for cancer patients.…”

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confidence: 99%

Interleukin‐6/STAT3 signaling as a promising target to improve the efficacy of cancer immunotherapy

et al. 2017

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Overcoming the immunosuppressive state in tumor microenvironments is a critical issue for improving the efficacy of cancer immunotherapy. Interleukin (IL)‐6, a pleiotropic cytokine, is highly produced in the tumor‐bearing host. Previous studies have indicated that IL‐6 suppresses the antigen presentation ability of dendritic cells (DC) through activation of signal transducer and activator of transcription 3 (STAT3). Thus, we focused on the precise effect of the IL‐6/STAT3 signaling cascade on human DC and the subsequent induction of antitumor T cell immune responses. Tumor‐infiltrating CD11b+ CD11c+ cells isolated from colorectal cancer tissues showed strong induction of the IL‐6 gene, downregulated surface expression of human leukocyte antigen (HLA)‐DR, and an attenuated T cell‐stimulating ability compared with those from peripheral blood mononuclear cells, suggesting that the tumor microenvironment suppresses antitumor effector cells. In vitro experiments revealed that IL‐6‐mediated STAT3 activation reduced surface expression of HLA‐DR on CD14+ monocyte‐derived DC. Moreover, we confirmed that cyclooxygenase 2, lysosome protease and arginase activities were involved in the IL‐6‐mediated downregulation of the surface expression levels of HLA class II on human DC. These findings suggest that IL‐6‐mediated STAT3 activation in the tumor microenvironment inhibits functional maturation of DC to activate effector T cells, blocking introduction of antitumor immunity in cancers. Therefore, we propose in this review that blockade of the IL‐6/STAT3 signaling pathway and target molecules in DC may be a promising strategy to improve the efficacy of immunotherapies for cancer patients.

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confidence: 99%

Interleukin‐6/STAT3 signaling as a promising target to improve the efficacy of cancer immunotherapy

et al. 2017

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“…Peptide Vaccines So far, peptide vaccines aim to elicit and expand tumor-specific T cells capable to control or eradicate the tumor and may be more efficacious in patients with minimal residual disease than in patients with broadly disseminated metastatic disease [24]. Despite the high expectation based on preclinical studies, the results of preliminary studies using peptide vaccines have been disappointing.…”

Section: Other Immune Strategiesmentioning

confidence: 95%

Immunotherapy of Esophageal Cancer: Current Status, Many Trials and Innovative Strategies

2018

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The majority of patients with esophageal cancer present with advanced disease and chemotherapy is the mainstay of palliation. However, efficacy is limited by the development of chemotherapy resistance and treatment options beyond first- and second-line treatment are scarce. Immunotherapy is a novel treatment option that has shown encouraging efficacy in several types of cancer, also in esophageal cancer. In esophageal squamous cell cancer (ESCC), early phase evaluation of immune checkpoint inhibitors has yielded promising results, however, results from phase 3 trials are currently still lacking. Besides checkpoint inhibitors, other immunogenic approaches e.g. peptide vaccines, adoptive T-cell therapy and oncolytic viruses are under development. This review describes the biological rational for immunotherapy and provides first accumulating data on its use in advanced esophageal cancer, with a focus on ESCC.

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“…as assessed in Gros et al 2016; Linnemann et al 2015; McGranahan et al 2016; Pritchard et al 2015a; Robbins et al 2013; Schmidt et al 2017; Snyder et al 2014; van Rooij et al 2013). The possible reasons behind suboptimal immunogenicity of peptide vaccines for cancer are reviewed by Kumai et al (2017). …”

Section: Identification Of Neoantigensmentioning

confidence: 99%

Identifying neoantigens for use in immunotherapy

Hutchison

Pritchard

2018

Mamm Genome

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This review focuses on the types of cancer antigens that can be recognised by the immune system and form due to alterations in the cancer genome, including cancer testis, overexpressed and neoantigens. Specifically, neoantigens can form when cancer cell-specific mutations occur that result in alterations of the protein from 'self'. This type of antigen can result in an immune response sufficient to clear tumour cells when activated. Furthermore, studies have reported that the likelihood of successful immunotherapeutic targeting of cancer by many different methods was reliant on immune response to neoantigens. The recent resurgence of interest in the immune response to tumour cells, in conjunction with technological advances, has resulted in a large increase in the predicted, identified and functionally confirmed neoantigens. This growth in identified neoantigen sequences has increased the contents of training sets for algorithms, which in turn improves the prediction of which genetic mutations may form neoantigens. Additionally, algorithms predicting how proteins will be processed into peptide epitopes by the proteasome and which peptides bind to the transporter complex are also improving with this research. Now that large screens of all the tumour-specific protein altering mutations are possible, the emerging data from assessment of the immunogenicity of neoantigens suggest that only a minority of variants will form targetable epitopes. The potential for immunotherapeutic targeting of neoantigens will therefore be greater in cancers with a higher frequency of protein altering somatic variants. There is considerable potential in the use of neoantigens to treat patients, either alone or in combination with other immunotherapies and with continued advancements, these potentials will be realised.

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Peptide vaccines in cancer — old concept revisited

Cited by 98 publications

References 69 publications

Interleukin‐6/STAT3 signaling as a promising target to improve the efficacy of cancer immunotherapy

Interleukin‐6/STAT3 signaling as a promising target to improve the efficacy of cancer immunotherapy

Immunotherapy of Esophageal Cancer: Current Status, Many Trials and Innovative Strategies

Identifying neoantigens for use in immunotherapy

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