Glioblastoma is the most common primary brain tumor in adults. While many patients achieve disease remission following treatment with surgical resection, radiation therapy and chemotherapy, this remission is brief and invariably followed by tumor recurrence and progression. The failure to offer durable therapies to patients with glioblastoma reflects the complex nature of this cancer. Targeted therapies involving monoclonal antibodies (mAbs) have had remarkable success in various diseases including cancer. Unfortunately, the current targeted therapy for glioblastoma, bevacizumab, has had disappointing clinical results. There is a clear need for alternative targeted therapies for glioblastoma that can potentially improve overall survival of newly diagnosed patients. This proposal is intended to further develop an antibody against a cancer-specific antigen that has shown promising clinical results in humans. We will be exploring the possibility that the non-fucosylated mAb variant will have enhanced ADCC activity in vitro that will ultimately translate into enhanced therapeutic benefit in animal models. This research will be the first time that a non-fucosylated mAb will be evaluated in the context of brain malignancy.
The focus of this proposal is glioblastoma although other brain and non-brain cancers could be potential targets in the future. There is a clear unmet need for new therapies that can improve the prognosis for glioblastoma. New antibody therapies may offer an improved prognosis as a result of enhanced access to the brain, a more potent and specific tumor epitope, enhanced recruitment of antibody dependent cellular cytotoxicity, or some combination of these mechanisms.