Vaccination Effect of Interleukin‐6‐producing Pancreatic Cancer Cells in Nude Mice: A Model of Tumor Prevention and Treatment in Immune‐compromised Patients

In an effort to explore properties important in hematogenous metastasis of pancreatic adenocarcinoma, we previously demonstrated that tumor‐derived interleukin (IL)‐6 is a crucial factor that conveys resistance to liver metastasis. Here we extend the study to examine a possible vaccination effect of tumor‐derived IL‐6 in T‐cell‐deficient nude mice, as a model for predicting the effect in immune‐compromised patients. We used a pair of IL‐6‐nonproducing and highly producing pancreatic adenocarcinoma cell lines, PCI‐43 and PCI‐43h, respectively. The reaction intensity of anti‐PCI IgG antibodies in host nude mice was maximal 28 days after inoculation of PCI‐43h cells, and remained high thereafter. A fraction of the pancreatic carcinoma cell lines, namely, PCI‐6, ‐10, and ‐43, expressed surface antigenic determinant(s) reactive with the IgG; but the others, PCI‐19, ‐24, ‐55, ‐64, ‐66, ‐68, ‐72, and ‐79, did not. Inoculation of PCI‐43h but not PCI‐43 suppressed growth of simultaneously inoculated PCI‐43, but not PCI‐24 xenografts. In addition, administration of PCI‐43h, but not PCI‐43 suppressed the growth of PCI‐43 that was xenografted 4 weeks later, thus revealing a vaccination effect of IL‐6‐producing PCI‐43h, but not IL‐6‐nonproducing PCI‐43. These data, obtained from T‐cell‐deficient nude mice, suggest an in vivo role for IL‐6 in inducing IgG‐mediated, pancreatic carcinoma‐specific vaccination against a thymus‐independent antigen.