LARGE-SCALE MANUFACTURING OF TXU(ANTI-CD7)-POKEWEED ANTIVIRAL PROTEIN(PAP) IMMUNOCONJUGATE FOR CLINICAL-TRIALS

We have conjugated the murine monoclonal anti-CD7 antibody TXU to the plant hemitoxin pokeweed antiviral protein (PAP) to construct an effec tive immunotoxin against CD7 antigen positive hematologic malignancies , The scaled-up production and purification of TXU antibody, PAP toxin , and TXU-PAP immunotoxin permitted the manufacturing of a highly puri fied clinical-grade TXU-PAP preparation. In clonogenic assays, TXU-PAP elicited selective and potent cytotoxicity against CD7 antigen positi ve human leukemia cells and killed primary clonogenic leukemic cells f rom T-lineage acute lymphoblastic leukemia (ALL) patients. To our know ledge, this pre-IND work represents the first effort of producing a cl inical-grade PAP immunotoxin for treatment of T-lineage ALL, Since the CD7 antigen is also expressed on AML cells, TXU-PAP could also be use ful for the treatment of CD7 positive acute myeloid leukemia (AML) pat ients.