scFv-mediated delivery of truncated BID suppresses HER2-positive osteosarcoma growth and metastasis

Cancer Biol Ther. 2008 Nov;7(11):1717-22. doi: 10.4161/cbt.7.11.6727. Epub 2008 Nov 4.


Osteosarcoma is the most common primary malignant bone tumor, with high rates of metastasis. Here, we examined the expression of human epidermal growth factor receptor-2 (HER-2) in osteosarcoma cell lines with different metastatic potential, finding that the expression was correlated with metastasis of implanted tumors. We then introduced an expression vector encoding the e23sFv-PEA II-Bid Delta1-60 gene, composed of a HER2-specific single-chain antibody fused with domain II of Pseudomonas exotoxin A (PEA) and the carboxy end of truncated active Bid. We demonstrated that the e23sFv-PEA II-Bid Delta1-60 molecule selectively recognized and killed HER2-overexpressing osteosarcoma cells in vitro. Subsequently, we introduced the e23sFv-PEA II-bid Delta1-60 gene into BALB/c athymic mice bearing HER2-positive osteosarcomas using i.m. injections of liposome-encapsulated vector. Expression of the e23sFv-PEA II-Bid Delta1-60 gene suppressed tumor growth, significantly prolonged animal survival and inhibited metastasis, thereby suggesting it may represent a competitive approach to treating HER2/neu-positive osteosarcoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Apoptosis Inducing Factor / metabolism
  • BH3 Interacting Domain Death Agonist Protein / genetics*
  • BH3 Interacting Domain Death Agonist Protein / metabolism
  • ErbB Receptors / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Genetic Therapy / methods
  • HeLa Cells
  • Humans
  • Immunoglobulin Fragments / chemistry*
  • Liposomes / chemistry
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Metastasis
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism*
  • Osteosarcoma / therapy*
  • Receptor, ErbB-2 / biosynthesis*


  • Apoptosis Inducing Factor
  • BH3 Interacting Domain Death Agonist Protein
  • Immunoglobulin Fragments
  • Liposomes
  • ErbB Receptors
  • Receptor, ErbB-2