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A bispecific antibody directly induces lymphoma cell death by simultaneously targeting CD20 and HLA-DR.

AbstractPURPOSE:
Both CD20 and HLA-DR antigens are highly expressed on a variety of B-cell lymphomas and are therapeutic targets in antibody-based lymphoma therapy. The aim of this study was to evaluate the anti-tumor effect of a bispecific antibody CD20-HLA-DR DVD-Ig on B-cell lymphoma.
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.
AuthorsJing Zeng, Ran Liu, Jinjing Wang, Yi Fang
JournalJournal 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
PMID25773122 (Publication Type: Journal Article)
Chemical References
  • Antibodies, Bispecific
  • Antigens, CD20
  • HLA-DR Antigens
  • Immunoglobulin G
  • Rituximab
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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