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.