Phase I Trial of Dendritic Cell Vaccination and Temozolomide for Recurrent Glioblastoma Multiforme

The development of drug resistance is a major cause for the failure of chemotherapy in the treatment of cancer patients. We wish to explore the possibility that this therapeutic impasse can be overcome by appropriately sequenced immunotherapy and chemotherapy. We hypothesise that many of the proteins involved in developing drug resistance will be over-expressed in tumour tissue relative to normal tissue, and can therefore serve as targets for vaccine-induced immune attack. A course of immunotherapy designed to drive immune responses towards drug-induced proteins may therefore 'sensitise' tumour tissue to further chemotherapy by selectively removing drug-resistant cells. We wish to explore this possibility in patients with glioblastoma multiforme, as this aggressive disease recurs in all patients post-chemotherapy, and current salvage chemotherapies are ineffective. The aims of this safety trial are: 1) To investigate the feasibility of generating vaccines using surgically-removed tissue from patients who have recurred after treatment with the chemotherapeutic drug temozolomide 2) To investigate the feasibility and safety of administering these vaccines prior to, and during, subsequent rounds of temozolomide therapy 3) To investigate whether the vaccination procedure generated from temozolomide-exposed tissue sensitises progressing tumours to subsequent temozolomide.