| RRC ID |
63496
|
| 著者 |
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.
|
| タイトル |
Generation of a canine anti-canine CD20 antibody for canine lymphoma treatment.
|
| ジャーナル |
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.
|
| 巻・号 |
10(1)
|
| ページ |
11476
|
| 公開日 |
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
|
| リソース情報 |
| 遺伝子材料 |
CSII-CMV-MCS-IRES2-Bsd (RDB04385) |
