TP-3 immunotoxins improve antitumor activity in mice with osteosarcoma

Clin Orthop Relat Res. 2005 Jan:(430):142-8. doi: 10.1097/01.blo.0000137544.30200.b6.


We measured the antitumor activity of two types of TP-3 immunotoxins that target an antigen expressed in tumors associated with osteosarcoma. Development of novel agents for treatment of patients with osteosarcoma is important. We previously described a monovalent-disulfide-stabilized recombinant immunotoxin made from the TP-3 antibody. This agent is called TP-3(dsFv)-PE38 and is cytotoxic to human osteosarcoma cells in vitro. To improve antigen binding, we designed and produced a bivalent immunotoxin, TP-3(dsFv)2-PE38. We evaluated the activity of both molecules in vitro and in vivo using tumor-bearing mice. Compared with the monovalent TP-3 immunotoxin, the bivalent TP-3 immunotoxin showed an approximately sevenfold increase in cytotoxic activity against three osteosarcoma cell lines which react with the TP-3 monoclonal antibody. The apparent affinity of the bivalent TP-3 immunotoxin was 12-fold greater than that of the monovalent TP-3 immunotoxin. The antitumor activities of both TP-3 immunotoxins were measured using severe combined immunodeficient mice bearing osteosarcoma cell line OHS-M1 tumors. The dose at which the bivalent TP-3 immunotoxin produces complete regressions of tumors is (1/2) that of the monovalent TP-3 immunotoxin. Increasing the avidity of TP-3(dsFv)-PE38 significantly improves its cytotoxic activity in vitro and results in a twofold increase in antitumor activity in vivo. Because TP-3-based immunotoxins have good antitumor activity in mice, these molecules merit additional development for possible treatment of osteosarcoma in humans.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / immunology*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Humans
  • Immunotoxins / therapeutic use*
  • Mice
  • Mice, SCID
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / immunology*
  • Peptide Fragments / immunology
  • Peptide Fragments / therapeutic use*
  • Thymopoietins / immunology
  • Thymopoietins / therapeutic use*
  • Treatment Outcome
  • Xenograft Model Antitumor Assays / methods


  • Immunotoxins
  • Peptide Fragments
  • Thymopoietins
  • splenotritin