Antitumor activity of TP3(anti-p80)-pokeweed antiviral protein immunotoxin in hamster cheek pouch and severe combined immunodeficient mouse xenograft models of human osteosarcoma.
TP3-pokeweed antiviral protein (PAP) immunotoxin is directed against the p80 antigen on osteosarcoma cells. Previous studies have demonstrated that TP3-PAP kills clonogenic human osteosarcoma cells in vitro and shows significant antitumor activity in a murine soft tissue sarcoma model (P. M. Anderson, et al, Cancer Res., 55: 1321-1327, 1995.) In this study, we demonstrate that TP3-PAP elicits potent in vivo antitumor activity in a hamster cheek pouch model of human osteosarcoma. Furthermore, treatment with TP3-PAP at nontoxic dose levels significantly delayed the emergence and progression of leg tumors and markedly improved tumor-free survival in severe combined immunodeficient mice challenged with OHS human osteosarcoma cells. Thus, TP3-PAP may be useful in the treatment of poor risk osteosarcoma.
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Department of Biotherapy, Drug Discovery Program, Wayne Hughes Institute, St. Paul, Minnesota 55113, USA.
Waurzyniak
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Myers
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Uckun
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FM
D000818:Animals; D002610:Cheek; D006224:Cricetinae; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D008647:Mesocricetus; D051379:Mice; D016513:Mice, SCID; D009061:Mouth Mucosa; D009699:N-Glycosyl Hydrolases; D012516:Osteosarcoma / Q000628:therapy*; D010446:Peptide Fragments / Q000627:therapeutic use*; D010940:Plant Proteins / Q000627:therapeutic use*; D054789:Ribosome Inactivating Proteins, Type 1; D013946:Thymopoietins / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000922:Immunotoxins; D010446:Peptide Fragments; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D013946:Thymopoietins; C051920:splenotritin; D009699:N-Glycosyl Hydrolases; C024275:pokeweed antiviral protein