CYTOKINE-MEDIATED GENE-THERAPY FOR CANCER

Background: Significant interest has been generated in the gene therapy of cancer. One strategy involves tumor-directed cytokine gene transfer and its effects on tumor immunobiology. Methods: The authors review the current literature pertaining to cytokine gene therapy of cancer and provide a description of gene transfer methods currently being evaluated. Results: Several cytokine gene transfer models have been described involving at least 12 different cytokines. The introduction of cytokine genes into experimental animal tumors improves their ability to be recognized and destroyed by the host immune system. Certain cytokines will regulate phenotypic properties such as major histocompatibility complex antigens, immunosuppressive peptides, protooncogenes or endogenous cytokine production. Cytokine-transduced tumors attract an inflammatory exudate in vivo that generally results in tumor destruction. The nature of the infiltrate (lymphocytic, mononuclear, granulocytic) cannot always be predicted from the known biological properties of each cytokine. Untransduced bystander tumor cells are usually also destroyed. Some, but not all, cytokine transductions result in the generation of systemic major histocompatibility complex-restricted, tumor immunity. It has been hypothesized that the local continuous production of cytokines by tumor cells provides an optimal microenvironment for antigen recognition and the generation of T-cell immunity. Conclusions: These experimental observations hold promise for the clinical application of genetically engineered tumor vaccines.