Caruso M, Pham-Nguyen K, Kwong Y L, Xu B, Kosai K I, Finegold M, Woo S L, Chen S H
Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11302-6. doi: 10.1073/pnas.93.21.11302.
Recombinant adenoviral mediated delivery of suicide and cytokine genes has been investigated as a treatment for hepatic metastases of colon carcinoma in mice. Liver tumors were established by intrahepatic implantation of a poorly immunogenic colon carcinoma cell line (MCA-26), which is syngeneic in BALB/c mice. Intratumoral transfer of the herpes simplex virus type 1 thymidine kinase (HSV-tk) and the murine interleukin (mIL)-2 genes resulted in substantial hepatic tumor regression, induced an effective systemic antitumoral immunity in the host and prolonged the median survival time of the treated animals from 22 to 35 days. The antitumoral immunity declined gradually, which led to tumor recurrence over time. A recombinant adenovirus expressing the mIL-12 gene was constructed and tested in the MCA-26 tumor model. Intratumoral administration of this cytokine vector alone increased significantly survival time of the animals with 25% of the treated animals still living over 70 days. These data indicate that local expression of IL-12 may also be an attractive treatment strategy for metastatic colon carcinoma.
重组腺病毒介导的自杀基因和细胞因子基因传递已被研究作为治疗小鼠结肠癌肝转移的方法。通过肝内植入免疫原性差的结肠癌细胞系（MCA-26）在肝脏建立肿瘤，该细胞系在BALB/c小鼠中是同基因的。肿瘤内转移单纯疱疹病毒I型胸苷激酶（HSV-tk）和小鼠白细胞介素（mIL）-2基因导致肝脏肿瘤显著消退，在宿主中诱导有效的全身抗肿瘤免疫，并将治疗动物的中位生存时间从22天延长至35天。抗肿瘤免疫逐渐下降，导致肿瘤随时间复发。构建了表达mIL-12基因的重组腺病毒并在MCA-26肿瘤模型中进行测试。单独瘤内给予这种细胞因子载体显著延长了动物的生存时间，25%的治疗动物存活超过70天。这些数据表明，IL-12的局部表达也可能是转移性结肠癌的一种有吸引力的治疗策略。
