Identification of a candidate therapeutic antibody for treatment of canine B-cell lymphoma.
Vet Immunol Immunopathol
; 164(3-4): 148-59, 2015 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-25764941
ABSTRACT
B-cell lymphoma is one of the most frequently observed non-cutaneous neoplasms in dogs. For both human and canine BCL, the standard of care treatment typically involves a combination chemotherapy, e.g. "CHOP" therapy. Treatment for human lymphoma greatly benefited from the addition of anti-CD20 targeted biological therapeutics to these chemotherapy protocols; this type of therapeutic has not been available to the veterinary oncologist. Here, we describe the generation and characterization of a rituximab-like anti-CD20 antibody intended as a candidate treatment for canine B-cell lymphoma. A panel of anti-canine CD20 monoclonal antibodies was generated using a mouse hybridoma approach. Mouse monoclonal antibody 1E4 was selected for construction of a canine chimeric molecule based on its rank ordering in a flow cytometry-based affinity assay. 1E4 binds to approximately the same location in the extracellular domain of CD20 as rituximab, and 1E4-based chimeric antibodies co-stain canine B cells in flow cytometric analysis of canine leukocytes using an anti-canine CD21 antibody. We show that two of the four reported canine IgG subclasses (cIgGB and cIgGC) can bind to canine CD16a, a receptor involved in antibody-dependent cellular cytotoxicity (ADCC). Chimeric monoclonal antibodies were assembled using canine heavy chain constant regions that incorporated the appropriate effector function along with the mouse monoclonal 1E4 anti-canine CD20 variable regions, and expressed in CHO cells. We observed that 1E4-cIgGB and 1E4-cIgGC significantly deplete B-cell levels in healthy beagle dogs. The in vivo half-life of 1E4-cIgGB in a healthy dog was â¼14 days. The antibody 1E4-cIgGB has been selected for further testing and development as an agent for the treatment of canine B-cell lymphoma.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfoma de Células B
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Antígenos CD20
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Doenças do Cão
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Anticorpos Monoclonais
Tipo de estudo:
Diagnostic_studies
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Guideline
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Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Vet Immunol Immunopathol
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos