Our focus is on the identification of molecular markers/targets that are specific to brain tumors and are pharmaceutically tractable.
We have identified several markers/targets that are present in a majority of patients with glioblastoma multiforme (GBM), a brain tumor of dismal prognosis, but virtually absent in normal organs. One of theses markers/targets is IL13R-alpha-2, a restricted receptor for an immune regulatory cytokine, interleukin 13 (IL13). Interestingly, it is a cancer/testes-like tumor antigen. IL13R-alpha-2 is currently used, pre-clinically and clinically, in a variety of immunotherapy and gene therapy approaches. For example, the first generation of our IL13-based cytotoxins, recombinant proteins containing bacterial toxins that kill specifically cancer cells expressing IL13 receptors, is in Phase III clinical trials worldwide. IL13R-alpha-2 is a target for producing vaccines against GBM and a genetically modified IL13 is used in adoptive immunotherapy trials.
We have also documented over-expression and an increased activity of a subset of specific transcription factors, which may play a crucial role in GBM progression. Coincidentally, these transcription factors appear to be good targets for the development of vaccines against cancer. New immunotherapeutic strategies are being developed based on all these findings in order to improve significantly the outcome of patients with brain tumors.