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[Gene therapy and cancer: from concepts to clinical applications]
1Hôpital Paul-Brousse, Service d'Hématologie, Villejuif, France.
Abstract:
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.
Insights
Gene therapy offers new hope for treating advanced cancers, including metastatic disease, by targeting tumor cells directly or stimulating an immune response. This approach aims to overcome treatment resistance in difficult-to-cure malignancies.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Context:
- Current cancer treatments are effective for only 10% of leukemias, lymphomas, and solid tumors, particularly at metastatic stages.
- Tumor microenvironment and cellular characteristics contribute to resistance against conventional therapies.
- Gene therapy presents a promising alternative for locally advanced and systemically disseminated cancers.
Purpose:
- To explore the application of gene therapy in treating human cancers, focusing on overcoming treatment resistance.
- To discuss various gene therapy strategies, including local and systemic approaches.
- To analyze the conceptual basis and limitations of current gene therapy modalities for cancer treatment.
Summary:
- Local gene therapy involves injecting viral vectors or producer cells to target tumor cells, potentially sparing healthy cells (e.g., cell-cycle dependent retroviruses for brain tumors).
- Systemic gene therapy strategies include Virally Directed Enzyme Prodrug Therapy (VDEPT), ecotropic genic immunotherapy to boost local immune responses, and systemic antigenic gene therapy to induce tumor-specific immune rejection.
- These methods aim to enhance treatment efficacy for cancers resistant to traditional chemotherapy.
Impact:
- Gene therapy holds potential for treating a wider range of cancers, including those currently considered incurable.
- Advances in gene therapy could lead to more targeted and effective cancer treatments with potentially fewer side effects.
- Further research into the conceptual basis and limitations is crucial for clinical translation and improved patient outcomes.