Tumor regression induced by intratumor therapy with a disabled infectious single cycle (DISC) herpes simplex virus (HSV) vector, DISC/HSV/murine granulocyte-macrophage colony-stimulating factor, correlates with antigen-specific adaptive immunity

The Journal of Immunology : Official Journal of the American Association of Immunologists
Selman A AliRobert C Rees

Abstract

Direct intratumor injection of a disabled infectious single cycle HSV-2 virus encoding the murine GM-CSF gene (DISC/mGM-CSF) into established murine colon carcinoma CT26 tumors induced a significant delay in tumor growth and complete tumor regression in up to 70% of animals. Pre-existing immunity to HSV did not reduce the therapeutic efficacy of DISC/mGM-CSF, and, when administered in combination with syngeneic dendritic cells, further decreased tumor growth and increased the incidence of complete tumor regression. Direct intratumor injection of DISC/mGM-CSF also inhibited the growth of CT26 tumor cells implanted on the contralateral flank or seeded into the lungs following i.v. injection of tumor cells (experimental lung metastasis). Proliferation of splenocytes in response to Con A was impaired in progressor and tumor-bearer, but not regressor, mice. A potent tumor-specific CTL response was generated from splenocytes of all mice with regressing, but not progressing tumors following in vitro peptide stimulation; this response was specific for the gp70 AH-1 peptide SPSYVYHQF and correlated with IFN-gamma, but not IL-4 cytokine production. Depletion of CD8(+) T cells from regressor splenocytes before in vitro stimulation with th...Continue Reading

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Citations

Apr 8, 2004·International Journal of Cancer. Journal International Du Cancer·Selman AliNicola Brown
Jul 8, 2005·Cancer Immunology, Immunotherapy : CII·Deepak P AssudaniSelman A Ali
Jun 17, 2009·Parasite Immunology·S A AliR C Rees
Apr 10, 2003·Cancer Immunology, Immunotherapy : CII·Robert C ReesIan Spendlove
Aug 18, 2004·International Journal of Experimental Pathology·Robin Lachmann
Mar 24, 2006·Cancer Immunology, Immunotherapy : CII·Deepak P AssudaniRobert C Rees
Aug 7, 2003·Expert Review of Vaccines·Geng Li, Robert C Rees

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