183 interferon alpha gene transfer enhances antitumor activity of allogeneic hematopoietic stem cell transplantation against solid cancers

183 Interferon alpha Gene Transfer Enhances Antitumor Activity of Allogeneic Hematopoietic Stem Cell Transplantation Against Solid Cancers by liver mononuclear cells (MNCs) compared to splenoeytes The[.]

by liver mononuclear cells (MNCs) compared to splenoeytes The hepatic MNCs in these animals were found to be highly cytotoxic to NK-sensitive YAC-I and B 16 melanoma cells, but they had little effect on EL4 cells, which are NK-resistant Intravenous injection of AcMNPV induced NK cell proliferation in the liver and spleen and enhanced anti-tumor immunity in mice that had B 16 liver metastases Furthermore, such treatment increased the survival of C57BL/6, Ja281 -!" and IFN-y", mice that had been previously injected with B I6 tumor cells Furthermore, AcMNPV efficiently stimulates NK cell-mediated, anti-tumor immunity the strong immune response induced by AcNPV makes it a promising candidate for a novel, adjuvant-containing vaccine vehicle against infectious diseases I.Abe, 1~ etal , (2003) J Immunol 171: 1133-1139 2.Abe, T ct al , (2005) J Virol 79:2847-2858 3.Kitajima, M et aI., (2006) Bioehem Biophys Res Commun 343:378-384 181 Eradication of Multifocal Glioma in a Syngeneic Glioblastoma Multiforme with Ad-Flt3L and Ad-HSV1-TK Gwendalyn D King ,' A K M Ghulam Muhammad,' James F Curtin,' Carlos Barcia,' Mariana Puntel,' Chunyan Liu,' Sarah B Honig, I Mari anela Candolfi,' Sonali Mondkar, I Pedro R Lowenstein,' Maria G Castro.' 'Gene Therapeutics Research Institute, Cedar Sinai Medical Center/University a/California Los Angeles, Los Angeles, CA The disseminated nature of human glioblastoma multi forme (GBM) makes it a particularly difficult tumor to treat Most preclinical models ofGBM involve treatment ofa single tumor mass when the human disease is characterized by infiltrating tumor cells which migrate from the primary tumor For therapeutic outcomes to translate from preclinical models into clinical trials, induction ofan antitumor response capable ofeliminating multi focal disease is essential We tested the hypothesis that adenoviral (Ad) mediated expression ofFlt3L and I·ISVI-TK within GBM would mediate regression of the primary, treated tumor mass and a secondary, untreated tumor growing at a distant site from the primary tumor and the site of therapeutic vector injection In either the single GBM or multifoeal GBM models used, all saline treated, control animals succumbed to tumors by day 22 Seventy percent of the animals bearing a single GBM mass treated with Ad-F1t3L and Ad-TK survived long-term Fifty percent of animals bearing both a large primary GBM and a second GBM in the contralateral hemisphere implanted at the time the primary tumor was being treated with Ad-Flt3L and Ad-TK also survived long-term (p