Adenovirus delivery provides extended XXXX exposure and augments treatment of @entity189 .

@entity137 @entity5 @entity19 @entity189 @entity1583 @entity12419
Type I interferons (e.g. IFNalpha2b) have been successfully used to treat a variety of @entity1583 , but have not been efficacious for treatment of most solid @entity5 . We tested the hypothesis that delivery of type I interferon utilizing recombinant adenovirus (rAd) vectors may improve treatment efficacy of metastatic @entity189 by providing increased interferon exposure resulting from continuous transgene expression. Treatment of @entity19 with a rAd-vector expressing hybrid-IFN (rAd-IFNalpha2alpha1) inhibited 4T1 mammary @entity5 growth and induced @entity5 regression in a dose-dependent manner. Moreover, rAd-IFNalpha2alpha1 treatment reduced hepatic and pulmonary metastatic burden. A comparison of local and systemic routes of administration demonstrated that intratumoral delivery of rAd-IFNalpha2alpha1 was sufficient for inhibition of @entity5 growth. Moreover, it reduced @entity137 associated with high-dose systemic IFNalpha2alpha1 exposure. Interestingly, antitumor activity following intratumoral treatment was due, in part, to the immunostimulatory capacity of the rAd vector component. Furthermore, systemic administration of rAd-IFNalpha2alpha1 potentiated the immunotherapeutic effect induced by local intralesional delivery of empty-rAd vector. These results suggest continuous @entity12419 exposure may provide improved antitumor responses for metastatic @entity189 . Additionally, immunostimulatory responses induced by rAd-IFNalpha2alpha1 may mitigate the immune-evasive @entity5 microenvironment.
