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169 Combination Oncolytic Herpes Simplex Virus and Dendritic Cell Immunotherapy for the Treatment of Established Murine Neuroblastomas ties in various cancer cell lines, including prostate cancer We a[.]
ties in various cancer cell lines, including prostate cancer We also reported that intratumoral administration of adcnoviral vector mediated Gliprl (AdGliprl) significantly reduced primary tumor and spontaneous lung metastasis in a preclinical mouse model of metastatic prostate cancer (Hum Gene Ther 14, 91-101 , 2003) These preclinical studies led to an ongoing neoadjuvant gene therapy Phase 1/11 clinical trial in which AdGLIPR I is being tested by direct intratumoral injection prior to radical prostatectomy (IND# 13033) Based on our ongoing studies ofGLlPR I function, we hypothesized that GLiPRI may promote macrophage mediated anti-tumoral activities In the current study, we analyzed the anti-tumoral activities ofGliprl gene modified Mfll METHODS: Peritoneal exudates Mfll were infected withAdGliprl or control Adv/CMV/Bgal24hr before use I-IBSS, uninfected Mfll, Bgal gene-modified Mfll (Bgal/Mfll), or Gliprl gene-modified Mfll (Gliprl/Mdi) were injected directly into orthotopic mouse prostate cancer (metastatic 178-2 BMA) on day after tumor cell inoculation At day 21, primary tumors and spontaneous lung metastasis were evaluated For survival analysis, animals were monitored daily and euthanized when moribund RESULTS: There were no significant differences in macrophage viability after transduction of AdGliprl compared with contro1 FACS analysis showed an increase in the number of cells positive for MI-ICc1assll antigen, CD40, and CD80 in Gllpr l/Mdi compared to uninfected Mfll or Bgal/Mfll IL-12 secretion from Gliprl/Msb in vitro was significantly increased compared to uninfected Mfll or Bgal/ Mfll GliprllMfll induced significant suppression of primary tumor growth (I 029mg) compared with Bgal/Mfll (2414mg) or uninfected Mfll (2691mg) (P