Antibody characterization using immunosignatures

Phillip Stafford, Stephen Albert Johnston, Orhun H. Kantarci, Ameneh Zare-Shahabadi, Arthur Warrington, Moses Rodriguez

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere0229080
JournalPloS one
Volume15
Issue number3
DOIs
StatePublished - Jan 1 2020

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Stafford, P., Johnston, S. A., Kantarci, O. H., Zare-Shahabadi, A., Warrington, A., & Rodriguez, M. (2020). Antibody characterization using immunosignatures. PloS one, 15(3), [e0229080]. https://doi.org/10.1371/journal.pone.0229080