Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20.

@article{citeulike:3021157, abstract = {Murine monoclonal antibody 2B8 specifically recognizes the CD20 phosphoprotein expressed on the surface of normal B lymphocytes and B-cell lymphomas. The light- and heavy-chain variable regions of 2B8 were cloned, after amplification by the polymerase chain reaction, into a cDNA expression vector that contained human IgG1 heavy chain and human kappa-light chain constant regions. High-level expression of chimeric-2B8 antibody (C2B8) was obtained in Chinese hamster ovary cells. Purified C2B8 exhibited antigen binding affinity and human-tissue reactivity similar to the native murine antibody. In vitro studies showed the ability of C2B8 to bind human C1q, mediate complement-dependent cell lysis of human B-lymphoid cell lines, and lyse human target cells through antibody-dependent cellular cytotoxicity. Infusion of macaque cynomolgus monkeys with doses ranging from 1.6 mg/kg to 6.4 mg/kg resulted in greater than 98\% depletion of peripheral blood (PB) B cells and 40\% to 70\% depletion of lymph node B cells. Recovery of PB B cells usually started at 2 weeks after treatment and required 60 to greater than 90 days to reach normal levels. As much as 95\% depletion of B cells in peripheral lymph nodes and bone marrow was observed following weekly injections of 16.8 mg/kg antibody. No toxicity was observed in any of the animals. These results offer the possibility of using an "immunologically active" chimeric anti-CD20 antibody as an alternative approach in the treatment of B-cell lymphoma.}, address = {IDEC Pharmaceuticals Corporation, San Diego, CA 92121.}, author = {Reff, M. E. and Carner, K. and Chambers, K. S. and Chinn, P. C. and Leonard, J. E. and Raab, R. and Newman, R. A. and Hanna, N. and Anderson, D. R. }, citeulike-article-id = {3021157}, issn = {0006-4971}, journal = {Blood}, keywords = {rituximab}, month = {January}, number = {2}, pages = {435--445}, posted-at = {2008-07-19 21:32:39}, priority = {2}, title = {Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/7506951}, volume = {83}, year = {1994} }

TY - JOUR ID - citeulike:3021157 L3 - citeulike-article-id:3021157 TI - Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. JF - Blood VL - 83 IS - 2 SP - 435 EP - 445 AD - IDEC Pharmaceuticals Corporation, San Diego, CA 92121. SN - 0006-4971 N2 - Murine monoclonal antibody 2B8 specifically recognizes the CD20 phosphoprotein expressed on the surface of normal B lymphocytes and B-cell lymphomas. The light- and heavy-chain variable regions of 2B8 were cloned, after amplification by the polymerase chain reaction, into a cDNA expression vector that contained human IgG1 heavy chain and human kappa-light chain constant regions. High-level expression of chimeric-2B8 antibody (C2B8) was obtained in Chinese hamster ovary cells. Purified C2B8 exhibited antigen binding affinity and human-tissue reactivity similar to the native murine antibody. In vitro studies showed the ability of C2B8 to bind human C1q, mediate complement-dependent cell lysis of human B-lymphoid cell lines, and lyse human target cells through antibody-dependent cellular cytotoxicity. Infusion of macaque cynomolgus monkeys with doses ranging from 1.6 mg/kg to 6.4 mg/kg resulted in greater than 98% depletion of peripheral blood (PB) B cells and 40% to 70% depletion of lymph node B cells. Recovery of PB B cells usually started at 2 weeks after treatment and required 60 to greater than 90 days to reach normal levels. As much as 95% depletion of B cells in peripheral lymph nodes and bone marrow was observed following weekly injections of 16.8 mg/kg antibody. No toxicity was observed in any of the animals. These results offer the possibility of using an "immunologically active" chimeric anti-CD20 antibody as an alternative approach in the treatment of B-cell lymphoma. KW - rituximab AU - Reff, ME AU - Carner, K AU - Chambers, KS AU - Chinn, PC AU - Leonard, JE AU - Raab, R AU - Newman, RA AU - Hanna, N AU - Anderson, DR PY - 1994/01/15/ UR - http://view.ncbi.nlm.nih.gov/pubmed/7506951 ER -