In vitro and in vivo kinetics of recombinant vaccinia virus cancer-gene therapy
Background. Gene therapy of cancer is a promising therapeutic modality. Recombinant vaccinia viruses (RecVV), engineered to produce cytokines, may be effective in this area. This study's purpose was to investigate the kinetics of RecVV infection, measuring protein production and in vivo viral growth pattern. Methods. RecVV were constructed by homologous recombination, encoding murine interleukin-2 (mIL-2). After tumor cell infection, mIL-2 production was measured in vitro. Tumor-bearing and naive hosts were inoculated with RecVV and wild type vaccinia. Livers, spleens, and (where applicable) tumors were sequentially harvested, and tissue viral levels were measured. Results. Infected tumor cells made high levels of mIL-2 after infection with RecVV encoding for this cytokine. Naive mice were able to clear recombinant but not wild type VV from their livers and spleens by days 3 and 5, respectively. Tumor-bearing animals had persistent RecVV titers in the tumor tissue at day 8. Conclusions. RecVV can infect tumor cells, causing the production of a large amount of foreign protein but are attenuated relative to wild type virus in the murine host.
Whitman, ED; Tsung, K; Paxson, J; Norton, JA; Shaked, A; Lyerly, HK
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