TOPICAL APPROACHES IN GENE-THERAPY IN CAR CINOMA OF PROSTATE - NOW SUFFICIENTLY WELL-TRIED FOR CLINICAL USE

The increasing availability of gene transfer techniques lends itself t o being used to optimize the immunotherapy and chemotherapy of advance d prostatic cancer. Preliminary trials are also aimed at correction of genetic defects leading to the expression of mutant gene products in the prostatic cancer. Several clinical immunogene therapy trials alrea dy approved by the FDA are underway. Among them the ex-vivo gene thera py protocols by: 1. GM-CSF-vaccine, making use of prostate cancer cell culture and retroviral vectors, 2. the IL-2 gene containing liposomes injected directly intratumorally (,,in situ vaccine''), and 3. PSA en coding vaccinia constructs whose goal is to induce an immune response to any cells expressing PSA. As an example of in-vivo gene therapy, th e transfer of Herpes simplex-thymidine kinase gene (HSV-tk) renders pr ostate cancer cells sensitive to subsequent gancyclovir-mediated cytot oxicity (suicide-gene-strategy). Another technique involving the trans fection of,,wild-type'' p53 or bet-ax genes into prostatic cancer cell s is thought to lower drug resistance and to facilitate chemotherapy b y mediation of apoptosis. The gene transfer experiments confirmed a ro le of retinoids in the growth and differentiation of normal and cancer ous prostate. Since most of the genes involved in prostatic cancerogen esis were unknown up to now, the substitution of mutated tumor suppres sor genes by their ,,wild-type'' counterparts and only blocking of pro tooncogenes by anti-sence oligo-nucleotides and ribozymes were possibl e in a few experiments. The future of corrective gene therapy will dep end on the development of highly efficient gene delivery systems with outstanding specificity for prostatic metastases.