Advances in gene therapy and immunotherapy for brain tumors.

Abstract

Treatments for malignant glioma, the most lethal and common primary brain tumor, are undergoing a dramatic evolution led by biological and technological advancements. This review focuses on developments in novel areas of gene therapy and immunotherapy, particularly vaccine development. Advances in basic research of antigen-presenting cells and applications of cytokines and immunogenic antigens have contributed to recent vaccine development for the treatment of intracranial malignant glioma. We have reviewed various vaccine designs, such as utilization of tumor antigen-loaded dendritic cells. Many immunotherapeutic manipulations require the use of recombinant genetic technologies. Here we present the findings on improved techniques for suicide gene therapy and various oncolytic viral therapies. Some of these constructs have induced an immune response at tumor sites in animal models of glioma. The intense investigation of therapies for glioma has made significant advances in designing diverse therapies with great potential. However, vaccine development has been hampered by the lack of universal tumor-specific antigens and a limited understanding of the mechanisms of tumor-induced immunosuppression. The success of gene therapy is limited by ineffective delivery systems and possible risk of infecting normal cells. As a result of the genetic heterogeneity of glioma cells and their invasive nature, future treatment approaches are likely to combine different agents in synergistic strategies that will hopefully be successful in stopping the growth and recurrence of glioma.