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Generation of a canine anti-canine CD20 antibody for canine lymphoma treatment
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Generation of a canine anti-canine CD20 antibody for canine lymphoma treatment
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Generation of a canine anti-canine CD20 antibody for canine lymphoma treatment
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Journal Article
Generation of a canine anti-canine CD20 antibody for canine lymphoma treatment
2020
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Animals
/ Antibodies, Anti-Idiotypic - immunology
/ Antibodies, Anti-Idiotypic - pharmacology
/ Antibody-dependent cell-mediated cytotoxicity
/ Antineoplastic Agents - immunology
/ Antineoplastic Agents - pharmacology
/ Dogs
/ Humanities and Social Sciences
/ Humans
/ Lymphoma
/ Lymphoma, Large B-Cell, Diffuse - drug therapy
/ Lymphoma, Large B-Cell, Diffuse - immunology
/ Lymphoma, Large B-Cell, Diffuse - pathology
/ Mice
/ Science
/ Survival
/ Tumors
