Soluble HLA-associated peptide from PSF1 has a cancer vaccine potency

Yoshida, Mari; Ishioka, Yukichi; Ozawa, Toshifumi; Okuyama, Hirohisa; Iguchi, Motofumi; Ota, Tsuguhito; Ito, Tsubasa; Nagira, Morio; Morita, Atsushi; Tanaka, Hidekazu; Naito, Hisamichi; Kidoya, Hiroyasu; Takakura, Nobuyuki

doi:10.1038/s41598-017-11605-2

Cited by 10 publications

(13 citation statements)

References 46 publications

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“…Soluble HLA molecules have been extensively used in investigating the immunopeptidome landscape in order to identify novel peptide candidates for therapeutic vaccines in the fields of cancer immunotherapy [ 123 , 124 ] and infectious diseases [ 125 , 126 , 127 , 128 ]. The use of soluble HLA for peptide isolation has been proposed as a valid alternative to immunoaffinity purification [ 119 ].…”

Section: In Vitro Methods For Hla Ligand Enrichmentmentioning

confidence: 99%

Uncovering the Tumor Antigen Landscape: What to Know about the Discovery Process

Feola

Chiaro

Martins

et al. 2020

Cancers

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According to the latest available data, cancer is the second leading cause of death, highlighting the need for novel cancer therapeutic approaches. In this context, immunotherapy is emerging as a reliable first-line treatment for many cancers, particularly metastatic melanoma. Indeed, cancer immunotherapy has attracted great interest following the recent clinical approval of antibodies targeting immune checkpoint molecules, such as PD-1, PD-L1, and CTLA-4, that release the brakes of the immune system, thus reviving a field otherwise poorly explored. Cancer immunotherapy mainly relies on the generation and stimulation of cytotoxic CD8 T lymphocytes (CTLs) within the tumor microenvironment (TME), priming T cells and establishing efficient and durable anti-tumor immunity. Therefore, there is a clear need to define and identify immunogenic T cell epitopes to use in therapeutic cancer vaccines. Naturally presented antigens in the human leucocyte antigen-1 (HLA-I) complex on the tumor surface are the main protagonists in evocating a specific anti-tumor CD8+ T cell response. However, the methodologies for their identification have been a major bottleneck for their reliable characterization. Consequently, the field of antigen discovery has yet to improve. The current review is intended to define what are today known as tumor antigens, with a main focus on CTL antigenic peptides. We also review the techniques developed and employed to date for antigen discovery, exploring both the direct elution of HLA-I peptides and the in silico prediction of epitopes. Finally, the last part of the review analyses the future challenges and direction of the antigen discovery field.

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Section: In Vitro Methods For Hla Ligand Enrichmentmentioning

confidence: 99%

Uncovering the Tumor Antigen Landscape: What to Know about the Discovery Process

Feola

Chiaro

Martins

et al. 2020

Cancers

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“…This allows for selection of robustly presented target antigens for peptide‐specific immunotherapy . Apart from that, a specific TAA of interest can be introduced, for example by transfection, and enables intensive studies of its HLA ligands . Infected cell cultures may also be used to identify HLA ligands derived from oncogenic viruses (Fig.…”

Section: Sources Of Tumour Human Leukocyte Antigen (Hla) Ligandsmentioning

confidence: 99%

“…39 In cell line-based approaches, sHLA molecules can be produced allowing direct isolation and subsequent identification of high peptide numbers without major differences concerning motifs, binding affinities, length, and the repertoire of HLA class I-presented peptides. 37,38,40,41 Working at mono-allelic resolution via transfection or transduction has proven to not only contribute significantly to unveiling HLA ligand motifs, 41,42 but also to improve (tumour) epitope prediction ( Fig. 1b).…”

Section: Artificial Models Of Human Tumoursmentioning

confidence: 99%

Mapping the tumour human leukocyte antigen (HLA) ligandome by mass spectrometry

2018

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The entirety of human leukocyte antigen (HLA)-presented peptides is referred to as the HLA ligandome of a cell or tissue, in tumours often termed immunopeptidome. Mapping the tumour immunopeptidome by mass spectrometry (MS) comprehensively views the pathophysiologically relevant antigenic signature of human malignancies. MS is an unbiased approach stringently filtering the candidates to be tested as opposed to epitope prediction algorithms. In the setting of peptide-specific immunotherapies, MS-based strategies significantly diminish the risk of lacking clinical benefit, as they yield highly enriched amounts of truly presented peptides. Early immunopeptidomic efforts were severely limited by technical sensitivity and manual spectra interpretation. The technological progress with development of orbitrap mass analysers and enhanced chromatographic performance led to vast improvements in mass accuracy, sensitivity, resolution, and speed. Concomitantly, bioinformatic tools were developed to process MS data, integrate sequencing results, and deconvolute multi-allelic datasets. This enabled the immense advancement of tumour immunopeptidomics. Studying the HLA-presented peptide repertoire bears high potential for both answering basic scientific questions and translational application. Mapping the tumour HLA ligandome has started to significantly contribute to target identification for the design of peptide-specific cancer immunotherapies in clinical trials and compassionate need treatments. In contrast to prediction algorithms, rare HLA allotypes and HLA class II can be adequately addressed when choosing MS-guided target identification platforms. Herein, we review the identification of tumour HLA ligands focusing on sources, methods, bioinformatic data analysis, translational application, and provide an outlook on future developments.

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“…Rather, it targets a CMG constituent with somewhat different ways and it is irrelevant to the regulation of the CMG action on DNA replication. Cancer immunotherapy triggers the immune system by recognizing molecular entities expressed specifically on the surface of cancer cells to eliminate these cells (Yoshida et al, 2017 ). Cytotoxic T lymphocytes (CTLs) attack cancer cells by recognizing cancer-specific antigenic peptides presented with human leukocyte antigen (HLA) on the cell surface.…”

Section: Strategies To Target the Cmg For Anticancer Therapymentioning

confidence: 99%

The Human Replicative Helicase, the CMG Complex, as a Target for Anti-cancer Therapy

Seo

Kang

2018

Front. Mol. Biosci.

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DNA helicases unwind or rearrange duplex DNA during replication, recombination and repair. Helicases of many pathogenic organisms such as viruses, bacteria, and protozoa have been studied as potential therapeutic targets to treat infectious diseases, and human DNA helicases as potential targets for anti-cancer therapy. DNA replication machineries perform essential tasks duplicating genome in every cell cycle, and one of the important functions of these machineries are played by DNA helicases. Replicative helicases are usually multi-subunit protein complexes, and the minimal complex active as eukaryotic replicative helicase is composed of 11 subunits, requiring a functional assembly of two subcomplexes and one protein. The hetero-hexameric MCM2-7 helicase is activated by forming a complex with Cdc45 and the hetero-tetrameric GINS complex; the Cdc45-Mcm2-7-GINS (CMG) complex. The CMG complex can be a potential target for a treatment of cancer and the feasibility of this replicative helicase as a therapeutic target has been tested recently. Several different strategies have been implemented and are under active investigations to interfere with helicase activity of the CMG complex. This review focuses on the molecular function of the CMG helicase during DNA replication and its relevance to cancers based on data published in the literature. In addition, current efforts made to identify small molecules inhibiting the CMG helicase to develop anti-cancer therapeutic strategies were summarized, with new perspectives to advance the discovery of the CMG-targeting drugs.

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Soluble HLA-associated peptide from PSF1 has a cancer vaccine potency

Cited by 10 publications

References 46 publications

Uncovering the Tumor Antigen Landscape: What to Know about the Discovery Process

Uncovering the Tumor Antigen Landscape: What to Know about the Discovery Process

Mapping the tumour human leukocyte antigen (HLA) ligandome by mass spectrometry

The Human Replicative Helicase, the CMG Complex, as a Target for Anti-cancer Therapy

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