Antibody characterization using immunosignatures.
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| Titel: | Antibody characterization using immunosignatures. |
|---|---|
| Autoren: | Stafford P; Department of Bioinformatics, Caris Life Sciences, Phoenix, Arizona, United States of America., Johnston SA; Center for Innovations in Medicine, Biodesign Institute, Arizona State University, Tempe, Arizona, United States of America., Kantarci OH; Department of Neurology, Mayo Clinic, Rochester, Minnesota, United States of America., Zare-Shahabadi A; Department of Neurology, Mayo Clinic, Rochester, Minnesota, United States of America., Warrington A; Department of Neurology, Mayo Clinic, Rochester, Minnesota, United States of America., Rodriguez M; Department of Neurology, Mayo Clinic, Rochester, Minnesota, United States of America. |
| Quelle: | PloS one [PLoS One] 2020 Mar 20; Vol. 15 (3), pp. e0229080. Date of Electronic Publication: 2020 Mar 20 (Print Publication: 2020). |
| Publikationsart: | Journal Article; Research Support, Non-U.S. Gov't |
| Sprache: | English |
| Info zur Zeitschrift: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: San Francisco, CA : Public Library of Science |
| MeSH-Schlagworte: | Peptide Library* , Protein Array Analysis*/methods, Antibodies, Monoclonal/*analysis , Epitope Mapping/*methods, Amino Acid Sequence ; Animals ; Antibodies, Monoclonal/isolation & purification ; Antibodies, Monoclonal/metabolism ; Antibody Specificity ; High-Throughput Screening Assays/methods ; Humans ; Immunoglobulin M/analysis ; Immunoglobulin M/metabolism ; Mice ; Peptides/chemistry ; Peptides/immunology ; Peptides/metabolism ; Protein Binding ; Proteome/analysis |
| Abstract: | Therapeutic monoclonal antibodies have the potential to work as biological therapeutics. OKT3, Herceptin, Keytruda and others have positively impacted healthcare. Antibodies evolved naturally to provide high specificity and high affinity once mature. These characteristics can make them useful as therapeutics. However, we may be missing characteristics that are not obvious. We present a means of measuring antibodies in an unbiased manner that may highlight therapeutic activity. We propose using a microarray of random peptides to assess antibody properties. We tested twenty-four different commercial antibodies to gain some perspective about how much information can be derived from binding antibodies to random peptide libraries. Some monoclonals preferred to bind shorter peptides, some longer, some preferred motifs closer to the C-term, some nearer the N-term. We tested some antibodies with clinical activity but whose function was blinded to us at the time. We were provided with twenty-one different monoclonal antibodies, thirteen mouse and eight human IgM. These antibodies produced a variety of binding patterns on the random peptide arrays. When unblinded, the antibodies with polyspecific binding were the ones with the greatest therapeutic activity. The protein target to these therapeutic monoclonals is still unknown but using common sequence motifs from the peptides we predicted several human and mouse proteins. The same five highest proteins appeared in both mouse and human lists. |
| Competing Interests: | The authors have declared that no competing interest exist. |
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| Substance Nomenclature: | 0 (Antibodies, Monoclonal) 0 (Immunoglobulin M) 0 (Peptide Library) 0 (Peptides) 0 (Proteome) |
| Entry Date(s): | Date Created: 20200321 Date Completed: 20200617 Latest Revision: 20200617 |
| Update Code: | 20250114 |
| PubMed Central ID: | PMC7083272 |
| DOI: | 10.1371/journal.pone.0229080 |
| PMID: | 32196507 |
| Datenbank: | MEDLINE |
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Nájsť tento článok vo Web of Science | Abstract: | Therapeutic monoclonal antibodies have the potential to work as biological therapeutics. OKT3, Herceptin, Keytruda and others have positively impacted healthcare. Antibodies evolved naturally to provide high specificity and high affinity once mature. These characteristics can make them useful as therapeutics. However, we may be missing characteristics that are not obvious. We present a means of measuring antibodies in an unbiased manner that may highlight therapeutic activity. We propose using a microarray of random peptides to assess antibody properties. We tested twenty-four different commercial antibodies to gain some perspective about how much information can be derived from binding antibodies to random peptide libraries. Some monoclonals preferred to bind shorter peptides, some longer, some preferred motifs closer to the C-term, some nearer the N-term. We tested some antibodies with clinical activity but whose function was blinded to us at the time. We were provided with twenty-one different monoclonal antibodies, thirteen mouse and eight human IgM. These antibodies produced a variety of binding patterns on the random peptide arrays. When unblinded, the antibodies with polyspecific binding were the ones with the greatest therapeutic activity. The protein target to these therapeutic monoclonals is still unknown but using common sequence motifs from the peptides we predicted several human and mouse proteins. The same five highest proteins appeared in both mouse and human lists. |
|---|---|
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0229080 |