Adenovirus-mediated gene transfer into tumors: evaluation of direct readministration of an adenoviral vector into subcutaneous tumors of immunocompetent mice

Because systemic administration of adenoviruses appears to be limited by th eir immunogenicity, we examined the feasibility of intratumoral administrat ion of adenoviruses. Direct intratumoral administration of adenoviruses res ulted in efficient but transient transgene expression. When adenoviruses we re readministered directly into tumors, reexpression of the transgene was a chieved. Transgene expression induced by the adenoviral readministration wa s, however, markedly weaker than that induced by the initial administration . Furthermore, intratumoral readministration of adenoviruses elicited profo und humoral and cellular immune responses to adenoviruses. These results ma y have important implications for efficacy considerations when adenoviral v ectors are used for clinical cancer gene therapy.