[Gene modified tumor vaccines in therapy of malignant melanoma]

Over the years the incidence of malignant melanoma in Poland as well as in other countries has been continuously increasing. Surgery is a treatment of choice in the early stages of primary lesions. Advanced malignant melanoma however is resistant to chemotherapy or radiotherapy. Therefore there is a need for new, more effective treatments. In the last years biotherapy such as immunotherapy is focusing a lot of attention. Unfortunately, systemic administration of immunostimulatory factors is very often associated with severe side effects. Thus, concepts of specific immunotherapies such as immunogene therapy have been developed. Currently, various gene therapy strategies of malignant melanoma are being evaluated in multiple clinical trials carried out all over the world. They include gene modified cancer vaccines (GMTV) modified with genes encoding (i) cytokines or (ii) costimulatory molecules and dendritic cells modified with (iii) genes encoding tumor antigens or (iv) immunostimulatory factors. Since January 1996 in Department of Cancer Immunology USOMS, at GreatPoland Cancer Center in Poznan, Poland a GMTV has been tested in malignant melanoma patients. For the last 6 years more than 220 patients were enrolled into study of GMTV consisting of melanoma cells modified with genes encoding IL-6 and its agonistic soluble receptor (sIL-6R). More than 25% of objective clinical responses and significant life extension were observed. The encouraging results formed a basis for design of a phase III prospective, randomized clinical study.