Reference - Detail
| RRC ID | 63496 |
|---|---|
| Author | Mizuno T, Kato Y, Kaneko MK, Sakai Y, Shiga T, Kato M, Tsukui T, Takemoto H, Tokimasa A, Baba K, Nemoto Y, Sakai O, Igase M. |
| Title | Generation of a canine anti-canine CD20 antibody for canine lymphoma treatment. |
| Journal | Sci Rep |
| 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. |
| Volume | 10(1) |
| Pages | 11476 |
| Published | 2020-7-10 |
| DOI | 10.1038/s41598-020-68470-9 |
| PII | 10.1038/s41598-020-68470-9 |
| PMID | 32651429 |
| PMC | PMC7351721 |
| MeSH | Animals Antibodies, Anti-Idiotypic / immunology Antibodies, Anti-Idiotypic / pharmacology* Antigens, CD20 / immunology* Antineoplastic Agents / immunology Antineoplastic Agents / pharmacology B-Lymphocytes Dog Diseases / drug therapy Dog Diseases / immunology Dog Diseases / pathology Dogs Humans Lymphoma / drug therapy* Lymphoma / immunology Lymphoma / veterinary Lymphoma, Large B-Cell, Diffuse / drug therapy* Lymphoma, Large B-Cell, Diffuse / immunology Lymphoma, Large B-Cell, Diffuse / pathology Mice |
| IF | 3.998 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 21 |
| Altmetric score changes over past 6months | 3.0 |
| Resource | |
| DNA material | CSII-CMV-MCS-IRES2-Bsd (RDB04385) |