In vitro and in vivo cytotoxicity of an anti-osteosarcoma immunotoxin containing pokeweed antiviral protein.
Successful treatment of many patients with osteosarcoma requires more effective chemotherapy. Since new agents are needed, we have developed an immunotoxin using TP-3, an IgG2b mAb which recognizes human and canine osteosarcomas and budding capillaries of tumors. The plant hemitoxin, pokeweed antiviral protein (PAP), was conjugated to TP-3 to produce an immunotoxin highly active against osteosarcoma. After 48 h no viable human OHS osteosarcoma cells were present in cultures containing TP-3-PAP as demonstrated by the absence of [3H]thymidine uptake into DNA. Furthermore, clonogenic assays indicated > 3.9 log kill of OHS at 18 h. The IC50 of TP-3-PAP against OHS was 3.5 +/- 1.0 (SD) x 10(-12) M. TP-3 mAb without PAP had no effect on OHS proliferation; PAP alone had no effect on OHS growth unless concentrations > 1000 pM were used. When TP-3-PAP (1.25 micrograms-10.0 micrograms) was given i.p. q.d. on days 3-5 after tumor inoculation, a dose-dependent reduction of the number of lung metastases was observed (P < 0.001). These results indicate that the TP-3-PAP immunotoxin may be useful in the treatment of osteosarcoma and some soft tissue sarcomas.
Anderson
P M
PM
Department of Pediatrics, University of Minnesota Biotherapy Program, Minneapolis 55455.
Meyers
D E
DE
Hasz
D E
DE
Covalcuic
K
K
Saltzman
D
D
Khanna
C
C
Uckun
F M
FM
D000818:Animals; D000951:Antigens, Neoplasm / Q000032:analysis; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009699:N-Glycosyl Hydrolases; D012516:Osteosarcoma / Q000276:immunology*; D000073718:Pancreatitis-Associated Proteins; D010940:Plant Proteins / Q000494:pharmacology*; D054789:Ribosome Inactivating Proteins, Type 1; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D000972:Antineoplastic Agents, Phytogenic; D000922:Immunotoxins; D000073718:Pancreatitis-Associated Proteins; D010940:Plant Proteins; C000612141:REG3A protein, human; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; C024275:pokeweed antiviral protein