Development of a T‐cell receptor multimer with high avidity for detecting a naturally presented tumor‐associated antigen on osteosarcoma cells

Watanabe, Kazue; Tsukahara, Tomohide; Toji, Shingo; Shogo, Saitoh; Hirohashi, Yoshihiko; Nakatsugawa, Munehide; Kubo, Terufumi; Kanaseki, Takayuki; Kameshima, Hidekazu; Terui, Takeshi; Sato, Noriyuki; Torigoe, Toshihiko

doi:10.1111/cas.13854

Cited by 8 publications

(9 citation statements)

References 20 publications

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“…To further study the immune response of T cells to neoantigens, we collected validated T-cell receptor-β (TCRβ) complementarity-determining region 3 (CDR3) sequences specific for tumor neoantigens (class I or II) and firstly constructed TCRβ-CDR3 sequence libraries. Eventually, we unified retrieved information and each entry was provided with cancer type, gene name, neoantigen sequence, CDR3 sequence, variable region of TCR (TRBV), diversity region of TCR (TRBD), and joining region of TCR (TRBJ) ( 36 ), as well as the reference links, if available in literatures.…”

Section: Methodsmentioning

confidence: 99%

dbPepNeo2.0: A Database for Human Tumor Neoantigen Peptides From Mass Spectrometry and TCR Recognition

Jian

et al. 2022

Front. Immunol.

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Neoantigens are widely reported to induce T-cell response and lead to tumor regression, indicating a promising potential to immunotherapy. Previously, we constructed an open-access database, i.e., dbPepNeo, providing a systematic resource for human tumor neoantigens to storage and query. In order to expand data volume and application scope, we updated dbPepNeo to version 2.0 (http://www.biostatistics.online/dbPepNeo2). Here, we provide about 801 high-confidence (HC) neoantigens (increased by 170%) and 842,289 low-confidence (LC) HLA immunopeptidomes (increased by 107%). Notably, 55 class II HC neoantigens and 630 neoantigen-reactive T-cell receptor-β (TCRβ) sequences were firstly included. Besides, two new analytical tools are developed, DeepCNN-Ineo and BLASTdb. DeepCNN-Ineo predicts the immunogenicity of class I neoantigens, and BLASTdb performs local alignments to look for sequence similarities in dbPepNeo2.0. Meanwhile, the web features and interface have been greatly improved and enhanced.

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Section: Methodsmentioning

confidence: 99%

dbPepNeo2.0: A Database for Human Tumor Neoantigen Peptides From Mass Spectrometry and TCR Recognition

Jian

et al. 2022

Front. Immunol.

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“…Target cell identification may be achieved through different approaches. One possibility is to stain tissue cells with fluorescent TCR multimers ( 89 ). We had co-cultured TCR hybridomas generated from lesional psoriatic CD8 + T cell clones with skin-specific cell types, which corresponded to the actual site of the immune response.…”

Section: Identification Of Tcr Epitopes In Hla-associated Autoimmune ...mentioning

confidence: 99%

Immunogenic self-peptides - the great unknowns in autoimmunity: Identifying T-cell epitopes driving the autoimmune response in autoimmune diseases

Prinz

2023

Front. Immunol.

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HLA-associated autoimmune diseases likely arise from T-cell-mediated autoimmune responses against certain self-peptides from the broad HLA-presented immunopeptidomes. The limited knowledge of the autoimmune target peptides has so far compromised the basic understanding of autoimmune pathogenesis. This is due to the complexity of antigen processing and presentation as well as the polyspecificity of T-cell receptors (TCRs), which pose high methodological challenges on the discovery of immunogenic self-peptides. HLA-class I molecules present peptides to CD8+ T cells primarily derived from cytoplasmic proteins. Therefore, HLA-class I-restricted autoimmune responses should be directed against target cells expressing the corresponding parental protein. In HLA-class II-associated diseases, the origin of immunogenic peptides is not pre-specified, because peptides presented by HLA-class II molecules to CD4+ T cells may originate from both extracellular and cellular self-proteins. The different origins of HLA-class I and class II presented peptides determine the respective strategy for the discovery of immunogenic self-peptides in approaches based on the TCRs isolated from clonally expanded pathogenic T cells. Both involve identifying the respective restricting HLA allele as well as determining the recognition motif of the TCR under investigation by peptide library screening, which is required to search for homologous immunogenic self-peptides. In HLA-class I-associated autoimmune diseases, identification of the target cells allows for defining the restricting HLA allotype from the 6 different HLA-class I alleles of the individual HLA haplotype. It furthermore limits the search for immunogenic self-peptides to the transcriptome or immunopeptidome of the target cells, although neoepitopes generated by peptide splicing or translational errors may complicate identification. In HLA class II-associated autoimmune diseases, the lack of a defined target cell and differential antigen processing in different antigen-presenting cells complicate identification of the HLA restriction of autoreactive TCRs from CD4+ T cells. To avoid that all corresponding HLA-class II allotypes have to be included in the peptide discovery, autoantigens defined by autoantibodies can guide the search for immunogenic self-peptides presented by the respective HLA-class II risk allele. The objective of this article is to highlight important aspects to be considered in the discovery of immunogenic self-peptides in autoimmune diseases.

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“…PBF A24.2 peptides are determined to activate CTLs from HLA-A24-positive patients with OS and therefore trigger immunity to eliminate tumor cells (152). A PBF TCRmultimer has been successfully created to recognize the naturally presented PBF peptide on HLA-A24 + PBF + OS cells (153). Although data about the usage of PBF-modified T cells in treating OS are not available, studies of this issue are critical, as suggested by the encouraging results with PBF's role in oncogenicity and immunogenicity.…”

Section: Tcr T Therapymentioning

confidence: 99%

Novel Immunotherapies for Osteosarcoma

Zhang

Chen

et al. 2022

Front. Oncol.

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Osteosarcoma (OS) is the most common primary malignant bone sarcoma mainly affecting adolescents and young adults, which often progresses to pulmonary metastasis and leads to the death of OS patients. OS is characterized as a highly heterogeneous cancer type and the underlying pathologic mechanisms triggering tumor progress and metastasis are incompletely recognized. Surgery combined with neoadjuvant and postoperative chemotherapy has elevated 5-year survival to over 70% for patients with localized OS tumors, as opposed to only 20% of patients with recurrence and/or metastasis. Therefore, novel therapeutic strategies are needed to overcome the drawbacks of conventional treatments. Immunotherapy is gaining momentum for the treatment of OS with an increasing number of FDA-approved therapies for malignancies resistant to conventional therapies. Here, we review the OS tumor microenvironment and appraise the promising immunotherapies available in the management of OS.

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Development of a T‐cell receptor multimer with high avidity for detecting a naturally presented tumor‐associated antigen on osteosarcoma cells

Cited by 8 publications

References 20 publications

dbPepNeo2.0: A Database for Human Tumor Neoantigen Peptides From Mass Spectrometry and TCR Recognition

dbPepNeo2.0: A Database for Human Tumor Neoantigen Peptides From Mass Spectrometry and TCR Recognition

Immunogenic self-peptides - the great unknowns in autoimmunity: Identifying T-cell epitopes driving the autoimmune response in autoimmune diseases

Novel Immunotherapies for Osteosarcoma

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