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Cancer Res ; 79(20): 5452-5456, 2019 Oct 15.
Article in English | MEDLINE | ID: mdl-31416842

ABSTRACT

Therapeutic anticancer vaccination has been adapted as an immunotherapy in several solid tumors. However, the selection of promising candidates from the total quantity of possible epitopes poses a challenge to clinicians and bioinformaticians alike, and very few epitopes have been tested in experimental or clinical settings to validate their efficacy. Here, we present a comprehensive database of predicted nonmutated peptide epitopes derived from genes that are overly expressed in a group of 32 melanoma biopsies compared with healthy tissues and that were filtered against expression in a curated list of survival-critical tissues. We hypothesize that these "self-tolerant" epitopes have two desirable properties: they do not depend on mutations, being immediately applicable to a large patient collective, and they potentially cause fewer autoimmune reactions. To support epitope selection, we provide an aggregated score of expected therapeutic efficiency as a shortlist mechanism. The database has applications in facilitating epitope selection and trial design and is freely accessible at https://www.curatopes.com. SIGNIFICANCE: A database is presented that predicts and scores antitumor T-cell epitopes, with a focus on tolerability and avoidance of severe autoimmunity, offering a supplementary epitope set for further investigation in immunotherapy.


Subject(s)
Antigens, Neoplasm/immunology , Databases, Protein , Epitopes, T-Lymphocyte , Melanoma/secondary , Neoplasm Proteins/immunology , Skin Neoplasms/immunology , Antigens, Neoplasm/genetics , Autoimmunity/genetics , Epitopes, T-Lymphocyte/genetics , Epitopes, T-Lymphocyte/immunology , Humans , Immune Tolerance/genetics , Immunotherapy , Melanoma/genetics , Melanoma/immunology , Melanoma/therapy , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , Peptides/genetics , Peptides/immunology , Skin Neoplasms/genetics , Skin Neoplasms/therapy , T-Lymphocytes, Cytotoxic/immunology , Tumor Escape/genetics , Melanoma, Cutaneous Malignant
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