Efficient tumor regression induced by genetically engineered tumor cells secreting interleukin-2 and membrane-expressing allogeneic MHC class I antigen.

摘要

PURPOSE: To analyze the immunotherapeutic potentials of genetically engineered tumor cells secreting IL-2 and a membrane-expressing allogeneic MHC class I molecule Kb in a murine hepatoma model. METHODS: In order to express both genes in coordination in the target cells, we constructed a polycistronic retroviral vector containing Kb, IL-2, and NeoR genes using two internal ribosome entry sites (IRES). Tumor growth was carried out by implantation of transduced tumor cells into mouse, while anti-tumor effects were demonstrated by the treatment of established tumors. The infiltrated cells were analyzed by immunohistochemistry. RESULTS: The combined effect of IL-2 secretion and alloantigen expression on immunostimulation was demonstrated by the rejection of transduced tumor cells. In the treatment of established tumors, the Kb/IL-2 co-expressing tumor cells induced strong anti-tumor immunity, superior to that induced by the single gene-transduced cells. The increased diversity of infiltrated cell types in tumor sites indicated that both a specific and non-specific immune response had been activated. CONCLUSION: Our study provides evidence that tumor cells with IL-2 secretion and membrane-expression of allogeneic MHC class I antigen are capable of inducing both strong tumor rejection and immunity.