Large scale manufacturing of B43(anti-CD19)-Genistein for clinical trials in leukemia and lymphoma

被引:9
作者
Myers, DE [1 ]
Sicheneder, A [1 ]
Clementson, D [1 ]
Dvorak, N [1 ]
Venkatachalam, T [1 ]
Sev, AR [1 ]
Chandan-Langlie, M [1 ]
Uckun, FM [1 ]
机构
[1] Wayne Hughes Inst, St Paul, MN USA
关键词
large scale manufacturing B43 (anti-CD19)-genistein; clinical trials; leukemia & lymphoma;
D O I
10.3109/10428199809068569
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We have conjugated the murine monoclonal anti-CD19 antibody B43 to the tyrosine kinase inhibitor genistein to construct an effective immunoconjugate against CD19 antigen positive hematologic malignancies. The scaled-up production and purification of B43 antibody, genistein, and B43-Genistein immunoconjugate permitted the manufacturing of a highly purified clinical-grade B43-Genistein preparation. In clonogenic assays, B43-Genistein elicited selective and potent cytotoxicity against CD19 antigen positive human leukemia cells. To our knowledge, this work represents the first effort of producing a clinical-grade genistein immunoconjugate for treatment of B-lineage leukemia and lymphoma.
引用
收藏
页码:329 / +
页数:11
相关论文
共 7 条
[1]   MEMBRANE-ASSOCIATED CD19-LYN COMPLEX IS AN ENDOGENOUS P53-INDEPENDENT AND BCL-2-INDEPENDENT REGULATOR OF APOPTOSIS IN HUMAN B-LINEAGE LYMPHOMA-CELLS [J].
MYERS, DE ;
JUN, X ;
WADDICK, KG ;
FORSYTH, C ;
CHELSTROM, LM ;
GUNTHER, RL ;
TUMER, NE ;
BOLEN, J ;
UCKUN, FM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (21) :9575-9579
[2]   PRODUCTION OF A POKEWEED ANTIVIRAL PROTEIN (PAP)-CONTAINING IMMUNOTOXIN, B43-PAP, DIRECTED AGAINST THE CD19 HUMAN B-LINEAGE LYMPHOID DIFFERENTIATION ANTIGEN IN HIGHLY PURIFIED FORM FOR HUMAN CLINICAL-TRIALS [J].
MYERS, DE ;
IRVIN, JD ;
SMITH, RS ;
KUEBELBECK, VM ;
UCKUN, FM .
JOURNAL OF IMMUNOLOGICAL METHODS, 1991, 136 (02) :221-238
[3]   BIOTHERAPY OF B-CELL PRECURSOR LEUKEMIA BY TARGETING GENISTEIN TO CD19-ASSOCIATED TYROSINE KINASES [J].
UCKUN, FM ;
EVANS, WE ;
FORSYTH, CJ ;
WADDICK, KG ;
AHLGREN, LT ;
CHELSTROM, LM ;
BURKHARDT, A ;
BOLEN, J ;
MYERS, DE .
SCIENCE, 1995, 267 (5199) :886-891
[4]  
UCKUN FM, 1985, J IMMUNOL, V134, P3504
[5]  
UCKUN FM, 1985, J IMMUNOL, V134, P2010
[6]  
UCKUN FM, 1993, J BIOL CHEM, V268, P21172
[7]  
UCKUN FM, 1996, J BIOL CHEM, V271, P6396