Large scale manufacturing of B43(anti-CD19)-genistein for clinical trials in leukemia and lymphoma.
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.
Wayne Hughes Institute, St. Paul, MN, USA.
D E
DE
Myers
A
A
Sicheneder
D
D
Clementson
N
N
Dvorak
T
T
Venkatachalam
A R
AR
Sev
M
M
Chandan-Langlie
F M
FM
Uckun
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019833:Genistein / Q000627:therapeutic use; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry* / Q000627:therapeutic use; D007938:Leukemia / Q000628:therapy; D008223:Lymphoma / Q000628:therapy; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D018796:Immunoconjugates; D019833:Genistein