Suppression of metastatic hemangiosarcoma by a parvovirus MVMp vector transducing the IP-10 chemokine into immunocompetent mice

Cancer Gene Ther. 2002 May;9(5):432-42. doi: 10.1038/sj.cgt.7700457.


We have previously shown that the growth of human tumor xenografts in immunodeficient mice can be efficiently suppressed upon infection with the autonomous parvovirus H-1 or with cytokine-transducing derivatives thereof. To further evaluate the benefits of implementing parvoviruses in cancer gene therapy, we have created a new recombinant vector, MVMp/IP-10, transducing the immunoactive, antiangiogenic chemokine IP-10, and used this virus to treat syngeneic tumors grown in immunocompetent mice. Intratumoral/intraperitoneal administration of only 3 x 10(7) replication units of MVMp/IP-10 per animal strongly inhibited the progression of established H5V cell-induced vascular tumors, a highly malignant mouse model for human cavernous hemangioma and Kaposi's sarcoma. Retardation of recurrent tumor growth and suppression of life-threatening metastatic dissemination to internal organs were accompanied by a striking delay in hemangioma-associated mortality. Parental MVMp did not have a significant effect under these conditions up to the dose of 10(10) infectious units/animal, but had strong antihemangiosarcoma activity when used to infect H5V cells ex vivo prior to implantation. In all cases, virus therapy was very well tolerated. Virus-induced suppression of hemangiosarcoma was dependent on host T cells and associated with intratumoral persistence of IFN gamma-expressing cytotoxic lymphocytes, and led to the reduced expression of hepatic plasminogen activator inhibitor-1 (PAI-1), a metastasis-linked marker. This proof of principle study demonstrates that MVMp/IP-10 can aid the treatment of vascular tumors and that autonomous parvovirus-based vectors can be considered potent tools for cancer gene therapy purposes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Separation
  • Cell Survival
  • Chemokine CXCL10
  • Chemokines, CXC / genetics*
  • Coloring Agents / pharmacology
  • Endothelium / cytology
  • Flow Cytometry
  • Genetic Therapy / methods*
  • Genetic Vectors*
  • Hemangiosarcoma / therapy*
  • Liver / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Minute Virus of Mice / genetics*
  • Neoplasm Metastasis
  • Parvovirus / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tetrazolium Salts / pharmacology
  • Thiazoles / pharmacology
  • Time Factors
  • Transcription, Genetic
  • Transgenes
  • Tumor Cells, Cultured


  • Chemokine CXCL10
  • Chemokines, CXC
  • Coloring Agents
  • Tetrazolium Salts
  • Thiazoles
  • thiazolyl blue