Development of Immunogene therapy using IL-6 for Pancreatic Cancer

人胰腺癌细胞产生的白细胞介素-6（IL-6）与裸鼠体内血液向肝脏转移的可能性呈负相关。将IL-6 cDNA转染到PCI-43中，PCI-43是我们培养的胰腺癌细胞系之一，其不产生IL-6并产生许多向肝脏的转移。IL-6高生产克隆（PCI-43 h）产生很少的转移; IL-6生产因此对转移具有直接影响，而分别为IL-6低生产者和IL-6非生产者的其它转染子（PCI-43 l和PCI-43 n）确实产生转移。在体外介导抗体依赖性细胞毒性（ADCC）的肿瘤反应性IgG在接种PCI-43 h的受体裸鼠的血清中检测到，但在给予PCI-43 l、PCI-43 n或亲本PCI-43的小鼠的血清中未检测到。此外，我们使用腺病毒载体测试了N116 Y在阻断胰腺癌细胞体内生长中的功效。将其中N116 Y表达由CEA启动子驱动的AdCEA-N116 Y直接注射到裸鼠的脾脏中显著抑制其肝转移瘤的生长。

Production of interleukin-6 (IL-6) by human pancreatic carcinoma cells inversely correlates with potentials for blood-borne metastasis to the liver in nude mice. IL-6 cDNA was transfected to PCI-43, one of our cultured pancreatic carcinoma cell lines that does not produce IL-6 and generates numerous metastases to the liver. An IL-6 high-producer clone (PCI-43h) generated few metastases; IL-6 production thus has a direct effect on metastasis, whereas other transfectants (PCI-43l and PCI-43n), which are IL-6 low-, and IL-6 non-producers, respectively, did generate metastases. Tumor-reactive IgG, which mediated antibody-dependent cellular cytotoxicity (ADCC) in vitro, was detected in sera from recipient nude mice inoculated with PCI-43h but not in sera from mice given PCI-43l, PCI-43n or parent PCI-43. In addition, we tested the efficacy of N116Y in blocking the in vivo growth of pancreatic cancer cells using an adenoviral vector. Direct injection of the AdCEA-N116Y in which N116Y expression is driven by the CEA promoter, into the spleen in nude mice suppressed their growth of liver metastases significantly.