In Vitro and in Vivo Cytotoxicity of an Anti-Osteosarcoma Immunotoxin Containing Pokeweed Antiviral Protein

Peter M. Anderson, Diane E. Hasz, Fatih M. Uckun, Dorothea E. Meyers, Daniel A Saltzman, Fatih M. Uckun, Chand Khanna

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

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) × 10− 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 μg-10.0 μg) was given ip. 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.

Original languageEnglish (US)
Pages (from-to)1321-1327
Number of pages7
JournalCancer Research
Volume55
Issue number6
StatePublished - Mar 15 1995

Fingerprint Dive into the research topics of 'In Vitro and in Vivo Cytotoxicity of an Anti-Osteosarcoma Immunotoxin Containing Pokeweed Antiviral Protein'. Together they form a unique fingerprint.

Cite this