Characterization of anti-canine CD20 antibody 4E1-7-B_f and comparison with commercially available anti-human CD20 antibodies.

in PloS one by Takuya Mizuno, Yukinari Kato, Toshihiro Tsukui, Masaya Igase

TLDR

  • The study finds that the anti-canine CD20 antibody 4E1-7-B_f exhibits superior functional activities in canine lymphoma treatment compared to an obinutuzumab biosimilar, with potential for clinical utility.

Abstract

This study characterizes the previously reported anti-canine CD20 antibody 4E1-7-B_f and compares this with commercially available anti-human CD20 antibodies, rituximab and an obinutuzumab biosimilar. While the obinutuzumab biosimilar exhibited binding to canine CD20 in a CD20-transduced cell line, canine B-cell lymphoma cell line (CLBL-1/luc), and canine CD21 + B cells from healthy dogs, functional assays revealed the superiority of 4E1-7-B_f in antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity activities over those of the obinutuzumab biosimilar. Epitope analysis suggested an extracellular region on canine CD20 targeted by 4E1-7-B_f. Furthermore, the lipid raft localization of CD20 in CLBL-1/luc cells by treatment with 4E1-7-B_f classified this antibody as a type II anti-CD20 antibody which works with strong ADCC activity, similar to the obinutuzumab biosimilar, unlike rituximab, a type I anti-CD20 antibody, whose main action is CDC activity. These findings underscore the potential clinical utility of 4E1-7-B_f, emphasizing the specificity, potency, and therapeutic promise in canine lymphoma treatment.

Overview

  • The study characterizes the previously reported anti-canine CD20 antibody 4E1-7-B_f and compares it to commercially available anti-human CD20 antibodies, rituximab and an obinutuzumab biosimilar.
  • The study aims to assess the binding and functional activities of the antibodies against canine CD20, as well as their epitope targeting and localization in canine cells.
  • The primary objective of the study is to evaluate the potential clinical utility of 4E1-7-B_f in treating canine lymphoma, compared to commercially available anti-CD20 antibodies.

Comparative Analysis & Findings

  • The obinutuzumab biosimilar exhibited binding to canine CD20, but functional assays revealed the superiority of 4E1-7-B_f in antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) activities.
  • Epitope analysis suggested an extracellular region on canine CD20 targeted by 4E1-7-B_f, and the antibody was classified as a type II anti-CD20 antibody with strong ADCC activity.
  • In contrast, rituximab, a type I anti-CD20 antibody, exhibited main CDC activity, whereas the obinutuzumab biosimilar and 4E1-7-B_f showed mixed ADCC and CDC activities.

Implications and Future Directions

  • The findings suggest the potential clinical utility of 4E1-7-B_f in treating canine lymphoma, highlighting its specificity, potency, and therapeutic promise.
  • Future studies could investigate the efficacy of 4E1-7-B_f in canine lymphoma treatment and compare it to currently available therapies.
  • The discovery of 4E1-7-B_f's epitope and localization opens up opportunities for further research into the mechanisms of CD20-targeting antibodies in canine lymphoma treatment.
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