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Immunoconjugates targeting cell-surface antigens have demonstrated clinical activity to enable regulatory approval in several solid and hematologic malignancies. We hypothesize that a rigorous and comprehensive surfaceome profiling approach to identify osteosarcoma-specific cell-surface antigens can similarly enable development of effective therapeutics in this disease. Herein, we describe an integrated proteomic and transcriptomic surfaceome profiling approach to identify cell-surface proteins that are highly expressed in osteosarcoma but minimally expressed on normal tissues. Using this approach, we identified targets that are highly expressed in osteosarcoma. Three targets, MT1-MMP, CD276, and MRC2, were validated as overexpressed in osteosarcoma. Furthermore, we tested BT1769, an MT1-MMP-targeted Bicycle toxin conjugate, in osteosarcoma patient-derived xenograft models. The results showed that BT1769 had encouraging antitumor activity, high affinity for its target, and a favorable pharmacokinetic profile. This confirms the hypothesis that our approach identifies novel targets with significant therapeutic potential in osteosarcoma.
Pubmed ID: 35312779
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Public database with millions of high-resolution images showing the spatial distribution of proteins in different normal human tissues and cancer types, as well as different human cell lines. The data is released together with application-specific validation performed for each antibody, including immunohistochemisty, Western blot analysis and, for a large fraction, a protein array assay and immunofluorescent based confocal microscopy. The database has been developed in a gene-centric manner with the inclusion of all human genes predicted from genome efforts. Search functionalities allow for complex queries regarding protein expression profiles, protein classes and chromosome location. Antibodies included have been analyzed using a standardized protocol in a single attempt without further efforts to optimize the procedure and therefore it cannot be excluded that certain observed binding properties are due to technical rather than biological reasons and that further optimization could result in a different outcome. Submission of antibodies: The Swedish Human Proteome Atlas (HPA) program, invites submission of antibodies from both academic and commercial sources to be included in the human protein atlas. All antibodies will be validated by the HPA-program by a standard procedure and antibodies that are accepted will be use in the tissue- profiling program to generate high-resolution immunohistochemistry images representing a wide spectrum of normal tissues and cancer types.
View all literature mentionsCommercial instrument and chemical vendor. Developer and manufacturer of specialized technological products for life science research and clinical diagnostics markets.
View all literature mentionsSoftware package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.
View all literature mentionsCell line HT-1080 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line U2OS is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MG-63 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name C.B-Igh-1/IcrTac-Prkdcscid from IMSR.
View all literature mentionsMus musculus with name NU/J from IMSR.
View all literature mentionsMus musculus with name C.B-Igh-1/IcrTac-Prkdcscid from IMSR.
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on February 28,2023. Software Python package that provides infrastructure to process data from high-throughput sequencing assays. While the main purpose of HTSeq is to allow you to write your own analysis scripts, customized to your needs, there are also a couple of stand-alone scripts for common tasks that can be used without any Python knowledge.
View all literature mentionsSoftware for identifying, characterizing, and quantifying proteins in biological samples. Can be used for range of proteomics workflows such as protein and peptide identification, PTM analysis, and isobaric mass tagging for quantification. Supports multiple database search algorithms and multiple dissociation techniques.
View all literature mentionsQuality control software that perform checks on raw sequence data coming from high throughput sequencing pipelines. This software also provides a modular set of analyses which can give a quick impression of the quality of the data prior to further analysis.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsDatabase for the identification of the human proteome and its use across the scientific community. Users can browse proteins and chromosomes and contribute to the data repository.
View all literature mentionsSoftware designed to clean-up biosensor data. It can zero and crop data, align injection times, correct for DMSO effects and fit binding curves and offrates.
View all literature mentionsSoftware image analysis platform for quantitative tissue analysis in digital pathology by Indica Labs. Used for high-throughput, quantitative tissue analysis in oncology, neuroscience, metabolism, toxicology.
View all literature mentionsHuman and mouse genome annotation project which aims to identify all gene features in the human genome using computational analysis, manual annotation, and experimental validation.
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