[Gene therapy and cancer: from concepts to clinical applications].

The cure of human cancers at a micro- or macro-metastatic stage of the disease is restricted to chemocurable forms which represent only 10% of all leukemias, lymphomas and solid tumors. Local conditions in the tumor site and biological characteristics of tumor cells are responsible for the resistance to treatment of many malignant tumors. Gene therapy can be applied to locally incurable tumors as well as to systemically disseminated malignancies. Genic "Surgery" can be produced by local intra- or peritumoral injection of viral vectors and/or virus-producing cells. For example in the case of brain tumors the use of retroviruses which are cell-cycle dependent for the injection of target cells is expected to spare the non-cycling normal brain cells from the dividing tumor cells. Three main types of systemic gene therapy are presently under study: a) VDEPT (Virally Directed Enzyme Prodrug Therapy) attempts to induce the production of an enzyme which transforms a prodrug into a cytotoxic drug in the engineered tumor cells. b) Ecotropic genic immunotherapy (tumor-site directed immunotherapy) can be used to produce sufficient local concentrations of cytokines to induce antitumor immune response at the tumor site(s). c) Systemic antigenic gene therapy aims to induce tumor-specific antigens by transfection of tumor cells in order to initiate immune rejection of residual disease by the patient lymphocytic killer cells. The conceptual basis and the limitations of these therapeutic approaches are discussed.