O'Malley B W, Li D
Department of Otolaryngology-HNS, Johns Hopkins University, Baltimore, Maryland 21203-6402, USA.
Ann N Y Acad Sci. 1998 Apr 15;842:163-70. doi: 10.1111/j.1749-6632.1998.tb09644.x.
An established combination gene therapy strategy involving adenovirus vector delivery of the herpes thymidine kinase (tk) and murine interleukin-2 genes was adapted to treat salivary gland cancer in a murine model. Salivary tumors were generated by transcutaneous injection of 5 x 10(5) murine squamous carcinoma cells into the submandibular gland of syngeneic C3H/HeJ mice. After one week, established submandibular gland tumors were injected with a recombinant adenovirus containing therapeutic and control genes. Animals were subsequently administered ganciclovir twice daily (25 mg/kg) for six days. All animals receiving tk and ganciclovir demonstrated tumor regression, however a significantly greater response was seen in mice that were treated with both tk + mIL-2. Residual tumors from all treatment and control groups were harvested for microscopic evaluation and immunohistochemistry staining. Specific immunostaining revealed a predominance of CD8+ lymphocytes in the tumor beds of the animals treated with IL-2, suggesting a preferential immune response resulting from the local IL-2 expression. Although still in its infancy, the concept or using adenoviral gene therapy strategies to provide less invasive means of treating salivary tumors is promising.
一种既定的联合基因治疗策略，即将疱疹胸苷激酶（tk）基因和小鼠白细胞介素-2基因通过腺病毒载体递送，被应用于小鼠模型中治疗唾液腺癌。通过将5×10⁵个小鼠鳞状癌细胞经皮注射到同基因C3H/HeJ小鼠的下颌下腺来产生唾液腺肿瘤。一周后，向已形成的下颌下腺肿瘤注射含有治疗性基因和对照基因的重组腺病毒。随后，动物每天接受两次更昔洛韦（25mg/kg）治疗，持续六天。所有接受tk基因和更昔洛韦治疗的动物均出现肿瘤消退，然而，同时接受tk + mIL-2治疗的小鼠反应更为显著。收集所有治疗组和对照组的残留肿瘤用于显微镜评估和免疫组织化学染色。特异性免疫染色显示，在接受IL-2治疗的动物肿瘤床中CD8⁺淋巴细胞占优势，这表明局部IL-2表达引发了优先的免疫反应。尽管腺病毒基因治疗策略仍处于起步阶段，但利用其提供侵入性较小的唾液腺肿瘤治疗手段这一概念很有前景。
