Nagao S, Kuriyama S, Okuda H, Tominaga K, Nakatani T, Tsujinoue H, Yoshiji H, Fukui H
Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Int J Oncol. 2001 Jan;18(1):57-65.
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.
由于腺病毒的全身给药似乎受到其免疫原性的限制，我们研究了腺病毒瘤内给药的可行性。腺病毒直接瘤内给药导致高效但短暂的转基因表达。当腺病毒再次直接注射到肿瘤中时，实现了转基因的重新表达。然而，腺病毒再次给药诱导的转基因表达明显弱于初次给药诱导的表达。此外，腺病毒瘤内再次给药引发了对腺病毒的强烈体液免疫和细胞免疫反应。这些结果对于腺病毒载体用于临床癌症基因治疗时的疗效考量可能具有重要意义。
