Development of Immunogene therapy using IL-6 for Pancreatic Cancer

人胰腺癌细胞产生的白介素6(IL-6)与裸鼠肝脏血行转移的潜能呈负相关。将IL-6基因转移到我们培养的胰腺癌细胞系之一的pCI-43中，该细胞不产生IL-6，并产生大量的肝脏转移。IL-6高表达克隆(pCI-43h)产生的转移较少；因此，IL-6的产生对转移有直接影响，而其他转染体(pCI-43l和pCI-43n)分别是IL-6低产生和IL-6非产生，确实产生转移。在接种组裸鼠的血清中检测到肿瘤反应性的免疫球蛋白G，而在接种组、接种组和亲本接种组的血清中未检测到肿瘤反应性的免疫球蛋白。此外，我们用腺病毒载体检测了N116Y对胰腺癌细胞体内生长的阻断作用。将由CEA启动子驱动表达N116Y的AdCEA-N116Y直接注射到裸鼠的脾内，可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.