Gene therapy approaches in urologic oncology

The tools and concepts of cytokine gene-based immunotherapy are being applied to the development of potentially effective new adjuvant treatment modalities for urologic malignancies. In preclinical models for the most prevalent urologic cancers, such as renal cell, bladder, and prostate carcinoma, it was shown that cytokine secreting, growth inactivated, tumor cell preparations (1) are capable of inducing a T-cell response against even nonimmunogenic tumors, (2) have considerable therapeutic benefit in tumor bearing animals, and (3) establish effective immunologic memory in cured animals. These studies have advanced further our understanding of the efficacy and therapeutic use of cytokine secreting tumor cells and form the rationale for translating these preclinical results into a clinical setting. It is realistic to speculate that in the foreseeable future alternative or complementary approaches to cytokine gene-based immunotherapy will be developed that would augment immune responses in cancer patients. Genetically modified dendritic cells transduced with genes encoding isolated tumor rejection antigens or costimulatory signals, such as B7, may be even more potent immune stimulators to induce systemic immune responses. Although animal studies have shown considerable promise and investigational clinical trials are underway, additional research and further development still is required to realize the full benefit of this approach, and some forms of cancer eventually may respond to this form of cancer immunotherapy.