Glioblastoma multiforme (GBM) is the most aggressive brain tumor. Standard treatment includes surgery, radiation and chemotherapy. Prognosis is dismal with an average survival of approximately 1 year. Gliadel wafers are one treatment option, working as a source for local chemotherapy delivery. Their use is controversial with questionable survival benefit and potential side effects. We reviewed the literature in an effort to clarify their role in the treatment of high-grade gliomas. A systematic PubMed search was performed using the keywords 'Gliadel', 'carmustine' or 'BCNU wafers' in newly diagnosed high-grade glioma patients. Treatment regimen, and median survival were analyzed. Adverse event ratio was calculated by computing the number of adverse events in a study per patient receiving carmustine wafers. Nineteen studies with 795 patients were included in our review. Survival was 8.7-22.6 months with a mean overall survival (OS) of 16.2 months (control survival is approximately 14 months with surgery and adjuvant chemoradiotherapy). Adverse event ratio using Gliadel wafersin control group. Complication rate was 42.7%. Gliadel wafers may marginally increase survival and local control in newly diagnosed GBM patients but are associated with a high complication rate; therefore, we do not recommend using Gliadel wafers in patients with GBM. Further research may be warranted once a safer alternative to Gliadel wafers has been introduced.

In vivo electroporation has become a gold standard method for DNA immunization. The method assists the DNA entry into cells, results in expression and the display of the native form of antigens to professional cells of the immune system, uses both arms of immune system, has a built-in adjuvant system, is relatively safe, and is cost-effective. However, there are challenges for achieving an optimized reproducible process for eliciting strong humoral responses and for the screening of specific immune responses, in particular, when the aim is to mount humoral responses or to generate monoclonal antibodies via hybridoma technology. Production of monoclonal antibodies demands generation of high numbers of primed B and CD4 T helper cells in lymphoid organs needed for the fusion that traditionally is achieved by a final intravenous antigen injection. The purified antigen is also needed for screening of hundreds of clones obtained upon fusion of splenocytes. Such challenges make DNA vaccination dependent on purified proteins. Here, we have optimized methods for in vivo electroporation, production, and use of cells expressing the antigen and an in-cell Western screening method. These methods resulted in (1) reproducibly mounting robust humoral responses against antigens with different cell localizations, and (2) the ability to screen for antigen eliminating a need for protein/antigen purification. This process includes optimized parameters for in vivo electroporation, the use of transfected cells for final boost, and mild fixation/permeabilization of cells for screening. Using this process, upon two vaccinations via in vivo electroporation (and final boost), monoclonal antibodies against nucleus and cytoplasmic and transmembrane proteins were achieved.