In vivo and in vitro distribution of type 5 and fiber-modified oncolytic adenoviruses in XXXX blood compartments.

@entity5 @entity1 @entity4461
BACKGROUND: Successful @entity5 targeting of systemically administered oncolytic adenoviruses may be hindered by interactions with blood components. MATERIALS AND METHODS: Blood distribution of oncolytic adenoviruses featuring type 5 adenovirus fiber, 5/3 capsid chimerism, or RGD-4C in the fiber knob was investigated in vitro and in @entity1 with refractory solid @entity5 . RESULTS: Virus titers and prevalence in serum of @entity1 increased over the first post-treatment week, suggesting replication. Detection of low virus loads was more sensitive in @entity4461 than in serum, although viral levels > 500 viral particles/mL did not differ significantly between both sample types. While adenovirus bound to erythrocytes, platelets, granulocytes, and peripheral blood mononuclear cells in vitro, the virus was mainly detectable in erythrocytes and granulocytes in @entity5 @entity1 . Taken together with a temporary post-treatment decrease in thrombocyte counts, platelet activation by adenovirus and subsequent clearance seem likely to occur in @entity1 . Fiber modifications had limited observed effect on virus distribution in blood cell compartments. Neutrophils, monocytes and cytotoxic T lymphocytes were the major leukocyte subpopulations interacting with adenoviruses. CONCLUSION: Serum and @entity4461 are relevant to estimate oncolytic adenovirus replication. Insight into viral interactions with blood cells may contribute to the development of new strategies for @entity5 delivery.
