Immunological gene therapy approaches for malignant melanoma. 2. Preclinical studies and clinical strategies

Immuno-gene therapy approaches for the treatment of malignant melanoma are categorized into two major subgroups according to an active or passive immunological principle. Active immuno-gene therapy is subdivided into melanoma cell vaccines, DNA-based vaccinations and the treatment of pre-existing tumor tissue by cell-mediated or direct transfer of cytokine and/or cell surface signal genes. Passive immuno-gene therapy, employing an adoptive treatment with in vitro activated and expanded anti-tumor effector cells, involves two major application fields for gene transfer techniques, first the genetic modification of the effector cells, and second the in vivo amplification of pre-effector cells by procedures also used in active immuno-gene therapy. Corresponding preclinical studies are reviewed. The clinical studies inaugurated during the last few years are mostly still ongoing and focus on treatment safety and tolerability rather than efficacy. A recent trend is emerging to explore recombinant adenovirus and vaccinia virus vectors particularly with regard to in vivo gene transfer applications. Overall, immuno-gene therapy of melanoma is still in a highly experimental stage of development but may become a safe, efficacious and practical adjuvant treatment modality in the future.