410. Determinants of and Pharmacologic Modulation of Acute Toxicity Associated with Systemic Administration of First Generation and Helper-Dependent Adenoviral Vectors

What is it about?

Understanding how systemic administration of adenoviral (Ad) vectors elicits an acute host response is critical for human clinical gene therapy. Toxicity associated with systemic Ad administration is the result of a multi-phasic process. Early, acute toxicity is related to viral interaction with target cells and/or consequent vectors entry with viral uncoating. This process occurs rapidly within minutes to hours of vector administration. The activation of cytokines and thrombocytopenia associated with acute toxicity may result, at high doses, in disseminated intravascular coagulation and multi-organ damage. Intermediate toxicity, occurring from hours to days after injection, is less well defined and likely involves de novo cellular transcription and amplification of cytokine release and the systemic inflammatory response. Several days after Ad administration chronic toxicity may arise. It is primarily mediated by the host adaptive immune response to de novo production of antigens.

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Photo by svetjekolem on Unsplash

Photo by svetjekolem on Unsplash