Abstract | PURPOSE: METHODS: The gene for bispecific antibody CD20-HLA-DR DVD-Ig was constructed and expressed in FreeStyle™293-F cells, followed by purification. Their functions were characterized for binding to CD20 and HLA-DR and for cytotoxicity against B-cell lymphoma. RESULTS: The bispecific antibody CD20-HLA-DR DVD-Ig was engineered using the DNA fragments for the anti-CD20 rituximab and anti- HLA-DR hL243γ1. The CD20-HLA-DR DVD-Ig bound simultaneously to both CD20 and HLA-DR, induced potent complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) against B-cell lymphoma, and elicited homotypic adhesion and actin reorganization. Treatment of a mixture of human whole blood and Raji cells with CD20-HLA-DR DVD-Ig effectively depleted Raji cells and had a little toxicity against normal B cells. CONCLUSION: Our data indicated that targeting both CD20 and HLA-DR was an effective way against NHL, suggesting that CD20-HLA-DR DVD-Ig may be a promising therapeutic agent for B-cell lymphoma.
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Authors | Jing Zeng, Ran Liu, Jinjing Wang, Yi Fang |
Journal | Journal of cancer research and clinical oncology
(J Cancer Res Clin Oncol)
Vol. 141
Issue 11
Pg. 1899-907
(Nov 2015)
ISSN: 1432-1335 [Electronic] Germany |
PMID | 25773122
(Publication Type: Journal Article)
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Chemical References |
- Antibodies, Bispecific
- Antigens, CD20
- HLA-DR Antigens
- Immunoglobulin G
- Rituximab
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Topics |
- Antibodies, Bispecific
(genetics, immunology)
- Antibody Affinity
(immunology)
- Antibody-Dependent Cell Cytotoxicity
(immunology)
- Antigens, CD20
(immunology)
- Apoptosis
(immunology)
- Burkitt Lymphoma
(immunology, therapy)
- Cell Line, Tumor
- HEK293 Cells
- HLA-DR Antigens
(immunology)
- Humans
- Immunoglobulin G
(immunology)
- Protein Engineering
- Rituximab
(genetics, immunology)
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