Generation of a canine anti-canine CD20 antibody for canine lymphoma treatment

  • Sci Rep. 2020 Jul 10;10(1):11476. doi: 10.1038/s41598-020-68470-9.
Takuya Mizuno  1 ,  Yukinari Kato  2  3 ,  Mika K Kaneko  2 ,  Yusuke Sakai  4 ,  Toshinori Shiga  5 ,  Masahiro Kato  5 ,  Toshihiro Tsukui  5 ,  Hirofumi Takemoto  6 ,  Akio Tokimasa  6 ,  Kenji Baba  6 ,  Yuki Nemoto  7 ,  Osamu Sakai  7 ,  Masaya Igase  7
Affiliations
  • 1. Laboratory of Molecular Diagnostics and Therapeutics, The United Graduate School of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi, Yamaguchi Prefecture, 753-8515, Japan. [email protected].
  • 2. Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Miyagi, Japan.
  • 3. New Industry Creation Hatchery Center, Tohoku University, Miyagi, Japan.
  • 4. Laboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.
  • 5. Nippon Zenyaku Kogyo Co., Ltd., Koriyama, Fukushima, Japan.
  • 6. Laboratory of Veterinary Internal Medicine, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.
  • 7. Laboratory of Molecular Diagnostics and Therapeutics, The United Graduate School of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi, Yamaguchi Prefecture, 753-8515, Japan.
PMID: 32651429 DOI: 10.1038/s41598-020-68470-9
Abstract

Lymphoma is the most common hematological Cancer in dogs. Canine diffuse large B cell lymphoma shows a relatively good response to treatment with multi-agent cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy; however, the 2-year survival rate is as low as 20%. For human B cell type lymphoma, the anti-CD20 chimeric antibody, rituximab, was developed two decades ago. The combination of rituximab and CHOP chemotherapy was highly successful in improving patient prognosis. However, no anti-canine CD20 antibody is available for the treatment of canine lymphoma. During this study, a rat anti-canine CD20 monoclonal antibody was established. We also generated a rat-canine chimeric antibody against canine CD20 designed for clinical application. This chimeric antibody (4E1-7-B) showed in vitro antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against the canine B cell lymphoma cell line CLBL-1. Moreover, to obtain stronger ADCC activity, a defucosylated 4E1-7-B antibody (4E1-7-B_f) was also generated, and it showed tenfold stronger ADCC activity compared with 4E1-7-B. 4E1-7-B_f as well as 4E1-7-B suppressed the growth of CLBL-1 tumors in an immunodeficient xenotransplant mouse model. Finally, a single administration of 4E1-7-B_f induced considerable peripheral B cell depletion in healthy beagles. Thus, 4E1-7-B_f is a good antibody drug candidate for canine B cell type lymphoma.

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