Anti-VEGF single-chain antibody GLAF-1 encoded by oncolytic vaccinia virus significantly enhances antitumor therapy

Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12915-20. doi: 10.1073/pnas.0900660106. Epub 2009 Jul 15.


We previously reported that the replication-competent vaccinia virus (VACV) GLV-1h68 shows remarkable oncolytic activity and efficacy in different animal models as a single treatment modality and also in combination with chemotherapy [Yu YA, et al. (2009) Mol Cancer Ther 8:141-151]. Here, we report the construction of 3 VACV strains encoding GLAF-1, a previously undescribed engineered single-chain antibody (scAb). This unique scAb is transcribed from 3 vaccinia promoters (synthetic early, early/late, and late) and directed against both human and murine VEGFs. The expression of GLAF-1 was demonstrated in cell cultures. Also, the replication efficiency of all GLAF-1-expressing VACV strains in cell culture was similar to that of the parental GLV-1h68 virus. Successful tumor-specific delivery and continued production of functional scAb derived from individual VACV strains were obtained in tumor xenografts following a single intravenous injection of the virus. The VACV strains expressing the scAb exhibited significantly enhanced therapeutic efficacy in comparison to treatment of human tumor xenografts with the parental virus GLV-1h68. This enhanced efficacy was comparable to the concomitant treatment of tumors with a one-time i.v. injection of GLV-1h68 and multiple i.p. injections of Avastin. Taken together, the VACV-mediated delivery and production of immunotherapeutic anti-VEGF scAb in colonized tumors may open the way for a unique therapy concept: tumor-specific, locally amplified drug therapy in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / genetics*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Bevacizumab
  • Cell Line
  • Chlorocebus aethiops
  • Female
  • Humans
  • Male
  • Mice
  • Neoplasm Transplantation
  • Neoplasms, Experimental / blood supply
  • Neoplasms, Experimental / therapy*
  • Oncolytic Virotherapy*
  • Oncolytic Viruses / genetics*
  • Transplantation, Heterologous
  • Vaccinia virus / genetics*
  • Vaccinia virus / physiology
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / immunology*
  • Virus Replication


  • Antibodies
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Vascular Endothelial Growth Factor A
  • Bevacizumab