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In Vitro and in Vivo Cytotoxicity of an Anti-Osteosarcoma Immunotoxin Containing Pokeweed Antiviral Protein¹

Departments of Pediatrics [P. M. A., D. E. H., F. M. U.], Therapeutic Radiology [D. E. M., K. C., F. M. U.], Surgery [D. S.], and Small Animal Clinical Sciences [C. K.], University of Minnesota Biotherapy Program, Minneapolis Minnesota 55455

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 µg-10.0 µg) 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.

¹ This work was supported by the Children's Cancer Research Fund, The Hedberg Foundation, and The University of Minnesota Biotherapy Program.

² To whom requests for reprints should be addressed, at Division of Pediatric Hematology/Oncology, Box 484, University of Minnesota Hospital and Clinic, D557 Mayo, 420 Delaware Street SE, Minneapolis MN 55455.

Received 10/31/94. Accepted 1/16/95.

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