Fiber-mutant technique can augment gene transduction efficacy and anti-tumor effects against established murine melanoma by cytokine-gene therapy using adenovirus vectors

摘要: Abstract Melanoma cells are relatively resistant to adenovirus vector (Ad)-mediated gene transfer due the low expression of Coxsackie-adenovirus receptor (CAR), which acts as a primitive Ad-receptor. Therefore, extremely high doses Ad required for effective therapy against melanoma. In present study, we investigated whether fiber-mutant containing Arg-Gly-Asp (RGD) sequence in fiber knob could promote delivery and anti-tumor effects murine B16 BL6 tumor model. (in vitro) tumors vivo) infected with RGD necrosis factor α (Ad-RGD-TNFα) produced more TNFα than those conventional Ad-TNFα. addition, Ad-RGD-TNFα about one-tenth dosage Ad-TNFα induction equal therapeutic upon intratumoral injection into established tumors. Furthermore, combination both TNFα- interleukin 12-expressing Ads exhibited regression expressing each alone. These results suggested that altering Ad-tropism is very potent technology advancing