Immunotherapy and gene therapy for renal cell carcinoma

New immunotherapeutic strategies have significantly improved the management of metastatic renal cell carcinoma, which is otherwise refractory to conventional chemotherapy and radiotherapy. Objective response rates of up to 40% have been achieved in clinical trials using systemic administration of interferon-α, interleukin-2, adoptively-modified lymphokine-activated killer cells, or tumor-infiltrating lymphocytes. With the advent of recombinant genetics, approaches are now available for enhancing host antitumor immunity and improving tumor vaccine. In animal models, tumor vaccines expressing immunostimulatory cytokines have demonstrated the suppression of tumor growth and metastasis, elimination of pre-established tumors, and elicitation of immunity against tumor recurrence. However, most of these vaccines were not beneficial in human. Other approaches with the suppressor gene p53 and herpes simplex virus thymidine synthase gene as a suicide gene system have shown substantial tumor remission and clinical trials are currently underway. Gene therapy with multidrug resistance gene (MDR-1) also is applied for subsequent protection against myelosuppression during high-dose chemotherapy. Moreover, significant treatment improvements have resulted from combinations of gene therapy and immunotherapy along with cytotoxic agents, X irradiation, and biological response modifiers in experimental systems. In general, the future success of cancer gene therapy requires further development of techniques to regulate gene expression and enhancement of antitumor activity and choice of gene with appropriate bioactivity for individual tumors.