Gene therapy of cancer
Rosenthal, F.M.
CellGenix Technologie Transfer GmbH, Elsässerstr. 2n, D-79110 Freiburg, Germany
Department of Internal Medicine I (Hematology/Oncology), University Medical Center Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany
Cancer is rapidly becoming the leading medical cause of death in Western society. Even though important progress has been made using these therapeutic modalities alone or in combination in many types of cancer, treatment results have been stagnating in recent years especially in the more frequent cancers in spite of intensive clinical research. Better understanding of tumor pathogenesis and progress in molecular biology, cell biology and immunology, has now provided the foundation to develop new therapeutic strategies for patients with cancer. Gene therapy is the introduction of a gene into a cell which then produces the desired gene product and thus corrects a genetic defect or acquires a new function. Gene transfer into cells of therapeutic interest can be achieved by a variety of strategies using non-viral and viral methods. Potential strategies for gene therapy of cancer include corrections of the genetic defects by homologous recombination, antisense approaches, protection of non-neoplastic cells by transduction of resistance genes into normal cells and transfer of prodrug activating enzymes into tumor cells. Genetic marking of cells, like tumor infiltrating lymphocytes or hematopoietic stem cells allows to investigate the trafficking, survival and functional properties of the marked cell following adoptive transfer into the patient. We are persuing strategies (a) to activate specific effector cells of the immune system and (b) to expand unspecific effector cells of the hematopoietic system by introducing cytokine genes into tumor cells or into non-malignant bystander cells. Stimulated by the promising results obtained by numerous preclinical studies, we have initiated a phase I clinical trial in patients with advanced cancer using irradiated autologous tumor cells mixed with irradiated allogeneic IL-2 gene transfected fibroblasts as a vaccine. Apart from studying the feasability, safety and toxicity of the approach, we have obtained information about the potential biological and immunological effects of this strategy in man. Another gene therapeutic strategy, not only for patients with cancer, is the systemic production of therapeutic molecules in vivo by genetically modified cells. In mice with chemotherapy-induced cytopenia we have shown that a single injection of irradiated cytokine (G-CSF, GM-CSF) gene transfected fibroblasts was equally efficacious as twice daily s.c. injections for 7 days of the recombinant proteins. Several gene therapeutic strategies for patients with cancer have already made their way into early clinical trials. The study protocol has to be based on state-of-the-art scientific background and the preparations of somatic cell and gene therapy products indented for clinical use have to be done according to ‘good manufacturing practice’ guidelines. These guidelines require a high standard for cell processing and quality control. It is likely that in the future the direction of clinical trials will progress into combining different therapeutic approaches in order to maximize therapeutic efficacy.
| LOCATION |
DATE |
TIME |
| Lecture Hall II |
Tuesday, April 7 |
03:35 pm |