Epithelial cell adhesion molecule (EpCAM) is a type I transmembrane glycoprotein overexpressed in human epithelioma but with relatively low expression in normal epithelial tissues. To exploit this differential expression pattern for targeted cancer therapy, an EpCAM-targeted immunotoxin was developed and its antitumor activity was investigated in vitro. An immunotoxin (scFv2A9-PE or APE) was co...

A major obstacle in the successful delivery of antibody-based therapeutics to tumor cells is the heterogeneity of target antigen expression. We reported previously that retinoic acid (RA) is a potent and selective inducer of the cell-surface antigen CD38 in myeloid leukemia cells. The purpose of this study was to determine whether the RA-induced CD38 antigen could be a target for an anti-CD38-b...

Ricin A chain immunotoxin constructed with monoclonal antibody 791T/36, which recognizes a tumor associated glycoprotein Mr 72,000 antigen present on sarcomas and colon and ovarian cancer cells, is cytotoxic for cell lines from tumors expressing this antigen. Incubation of sarcoma 791T cells with immunotoxin for only 5 min is sufficient to produce greater than 95% inhibition of tumor cell growt...

Immunotoxin constructed by conjugating ricin A chain to monoclonal antibody 791T/36 specifically inhibits growth of human tumor xenografts which express the gp72 antigen recognized by the antibody component. Dose schedule tests showed that the major response was obtained during the first 5 days of treatment and further prolonged treatment did not improve therapy. Expression of gp72 antigen on t...

Recombinant immunotoxins are extremely promising agents for the targeted therapy of tumors with a certain molecular profile. In this work, we studied the properties of a new recombinant HER2-specific immunotoxin composed of the scFv antibody and a fragment of Pseudomonas exotoxin A (4D5scFv-PE40). High affinity of the immunotoxin for the HER2 tumor marker, its selective cytotoxicity against HER...

Immunotoxins have been suggested as possible therapeutic agents in patients with leptomeningeal carcinomatosis. The pharmacokinetics, stability, and toxicity of immunotoxins injected into the i.t. space were examined in rats and rhesus monkeys. Monoclonal antibodies specific for the human (454A12 and J1) and rat (OX26) transferrin receptors were coupled to recombinant ricin A chain. In monkeys,...

The delivery of cell-specific protein toxins to the interstitium of solid tumors was examined in athymic mice bearing s.c. human rhabdomyosarcoma (TE671) tumors. The toxins are diphtheria toxin (DT), Mr = 60,000, and an immunotoxin, Mr = 210,000. The immunotoxin is a chemical conjugate of a mutant DT defective in binding and a monoclonal antibody specific for the human transferrin receptor. The...

Monoclonal antibody 791T/36, recognizing a Mr 72,000 antigen on the surface of colon carcinoma cells, has been used to construct an immunotoxin by conjugating to it the ribosomal inhibitor protein, ricin toxin A chain. The antibody 791T/36 has been shown to bind to membranes of freshly disaggregated tumor cells from human colon tumors, and to localize in tumors in vivo. Subacute toxicology test...

A major problem encountered in the large-scale purification of the bivalent anti-T cell immunotoxin, A-dmDT390-bisFv(G4S), from Pichia pastoris supernatants was the presence of host glycoproteins exhibiting similar charge, size, and hydrophobicity characteristics. We overcame this problem by employing borate anion exchange chromatography. The borate anion has an affinity for carbohydrates and i...