38
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      An integrated database of experimentally validated major histocompatibility complex epitopes for antigen-specific cancer therapy

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Cancer immunotherapy represents a paradigm shift in oncology, offering a superior anti-tumor efficacy and the potential for durable remission. The success of personalized vaccines and cell therapies hinges on the identification of immunogenic epitopes capable of eliciting an effective immune response. Current limitations in the availability of immunogenic epitopes restrict the broader application of such therapies. A critical criterion for serving as potential cancer antigens is their ability to stably bind to the major histocompatibility complex (MHC) for presentation on the surface of tumor cells. To address this, we have developed a comprehensive database of MHC epitopes, experimentally validated for their MHC binding and cell surface presentation. Our database catalogs 451 065 MHC peptide epitopes, each with experimental evidence for MHC binding, along with detailed information on human leukocyte antigen allele specificity, source peptides, and references to original studies. We also provide the grand average of hydropathy scores and predicted immunogenicity for the epitopes. The database (MHCepitopes) has been made available on the web and can be accessed at https://github.com/jcm1201/MHCepitopes.git. By consolidating empirical data from various sources coupled with calculated immunogenicity and hydropathy values, our database offers a robust resource for selecting actionable tumor antigens and advancing the design of antigen-specific cancer immunotherapies. It streamlines the process of identifying promising immunotherapeutic targets, potentially expediting the development of effective antigen-based cancer immunotherapies.

          Abstract

          Statement of Significance: Current peptide-based cancer immunotherapy is challenged with the limited availability of immunogenic epitopes. To facilitate the discovery of immunogenic peptides, we developed a new, comprehensive database that contains both experimental and theoretical data on experimentally-verified MHC-binding epitopes.

          Related collections

          Most cited references25

          • Record: found
          • Abstract: found
          • Article: not found

          The blockade of immune checkpoints in cancer immunotherapy.

          Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            WebLogo: a sequence logo generator.

            WebLogo generates sequence logos, graphical representations of the patterns within a multiple sequence alignment. Sequence logos provide a richer and more precise description of sequence similarity than consensus sequences and can rapidly reveal significant features of the alignment otherwise difficult to perceive. Each logo consists of stacks of letters, one stack for each position in the sequence. The overall height of each stack indicates the sequence conservation at that position (measured in bits), whereas the height of symbols within the stack reflects the relative frequency of the corresponding amino or nucleic acid at that position. WebLogo has been enhanced recently with additional features and options, to provide a convenient and highly configurable sequence logo generator. A command line interface and the complete, open WebLogo source code are available for local installation and customization. Copyright 2004 Cold Spring Harbor Laboratory Press
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              A guide to cancer immunotherapy: from T cell basic science to clinical practice

              The T lymphocyte, especially its capacity for antigen-directed cytotoxicity, has become a central focus for engaging the immune system in the fight against cancer. Basic science discoveries elucidating the molecular and cellular biology of the T cell have led to new strategies in this fight, including checkpoint blockade, adoptive cellular therapy and cancer vaccinology. This area of immunological research has been highly active for the past 50 years and is now enjoying unprecedented bench-to-bedside clinical success. Here, we provide a comprehensive historical and biological perspective regarding the advent and clinical implementation of cancer immunotherapeutics, with an emphasis on the fundamental importance of T lymphocyte regulation. We highlight clinical trials that demonstrate therapeutic efficacy and toxicities associated with each class of drug. Finally, we summarize emerging therapies and emphasize the yet to be elucidated questions and future promise within the field of cancer immunotherapy.
                Bookmark

                Author and article information

                Contributors
                Journal
                Antib Ther
                Antib Ther
                anther
                Antibody Therapeutics
                Oxford University Press
                2516-4236
                April 2024
                17 June 2024
                17 June 2024
                : 7
                : 2
                : 177-186
                Affiliations
                Department of Precision Medicine, Terasaki Institute for Biomedical Innovation , Los Angeles, CA 90024, United States
                Department of Precision Medicine, Terasaki Institute for Biomedical Innovation , Los Angeles, CA 90024, United States
                Department of Pipeline Development , Biomap, Inc. , Palo Alto, CA 94303, United States
                Department of Precision Medicine, Terasaki Institute for Biomedical Innovation , Los Angeles, CA 90024, United States
                Quantitative and Computational Biology Department, University of Southern California , Los Angeles, CA 90089, United States
                Autonomy Research Center for STEAHM (ARCS) , California State University Northridge , Northridge, CA 91324, United States
                Department of Precision Medicine, Terasaki Institute for Biomedical Innovation , Los Angeles, CA 90024, United States
                Author notes
                Corresponding author. Department of Precision Medicine, Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90024, United States. E-mail: chongming.jiang@ 123456terasaki.org
                Author information
                https://orcid.org/0000-0003-2566-3313
                Article
                tbae011
                10.1093/abt/tbae011
                11200702
                38933532
                46f030f3-2a44-4cc6-ab27-ee051b9e4c6a
                © The Author(s) 2024. Published by Oxford University Press on behalf of Antibody Therapeutics.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 26 January 2024
                : 18 April 2024
                : 17 June 2024
                Page count
                Pages: 10
                Funding
                Funded by: National Institutes of Health, DOI 10.13039/100000002;
                Award ID: R01 DK119795
                Award ID: R35 GM122465
                Categories
                Emerging Targets of Therapeutic Antibodies for Immuno-Oncology
                AcademicSubjects/SCI01030
                AcademicSubjects/SCI00100

                major histocompatibility complex,epitopes,cancer immunotherapy,immunogenicity

                Comments

                Comment on this article

                scite_
                0
                0
                0
                0
                Smart Citations
                0
                0
                0
                0
                Citing PublicationsSupportingMentioningContrasting
                View Citations

                See how this article has been cited at scite.ai

                scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.

                Similar content223

                Most referenced authors590