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 their immunogenicity, we examined the feasibility of intratumoral administration of adenoviruses. Direct intratumoral administration of adenoviruses resulted in efficient but transient transgene expression. When adenoviruses were readministered directly into tumors, re-expression of the transgene was achieved. Transgene expression induced by the adenoviral readministration was, however, markedly weaker than that induced by the initial administration. Furthermore, intratumoral readministration of adenoviruses elicited profound humoral and cellular immune responses to adenoviruses. These results may have important implications for efficacy considerations when adenoviral vectors are used for clinical cancer gene therapy.
Nagao
S
S
Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Kuriyama
S
S
Okuda
H
H
Tominaga
K
K
Nakatani
T
T
Tsujinoue
H
H
Yoshiji
H
H
Fukui
H
H
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000917:Antibody Formation; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology / Q000628:therapy; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007111:Immunity, Cellular; D007121:Immunocompetence; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D019076:Transgenes / Q000235:genetics