Diffuse intrinsic pontine glioma (DIPG) is a devastating brain tumor in children with no long-term cure. Current therapies rely on radiation which provides only a brief respite from disease. Even when temporarily successful, the therapies themselves cause significant damage to healthy brain tissue. A significant unmet need is development of effective therapies that can be delivered non-invasively, are non-toxic for non-tumor tissues and do not cause inflammation within the central nervous system. We aim to generate a multi-functional antibody able to penetrate the blood-brain barrier and starve DIPG cells of essential nutrients. Cancer cells are notable for their rapid growth, which must...
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Diffuse intrinsic pontine glioma (DIPG) is a devastating brain tumor in children with no long-term cure. Current therapies rely on radiation which provides only a brief respite from disease. Even when temporarily successful, the therapies themselves cause significant damage to healthy brain tissue. A significant unmet need is development of effective therapies that can be delivered non-invasively, are non-toxic for non-tumor tissues and do not cause inflammation within the central nervous system. We aim to generate a multi-functional antibody able to penetrate the blood-brain barrier and starve DIPG cells of essential nutrients. Cancer cells are notable for their rapid growth, which must be supported by nutrients from blood vessels generated specifically to supply the tumor cells. As a result, antibodies that restrict blood vessel growth, such as the anti-vascular endothelial growth factor (VEGF-A) antibody Bevacizumab, have generated considerable interest for the treatment of glioblastoma. When given to patients with DIPG, Bevacizumab failed to show improved survival; presumably due to low antibody concentrations at the tumor site, low VEGF-A expression in early stages of disease and tumor resistance. We hypothesize that simultaneous targeting of VEGF-A and PlGF with a single antibody will improve therapeutic efficacy while remaining non-toxic. PlGF is not essential for non-tumor cells and is minimally expressed in healthy tissues; therefore this approach is expected to have few, if any, side effects. We plan to identify a panel of antibodies binding VEGF-A and PlGF and preventing their interactions with the cellular receptors that trigger tumor growth. Next, we will engineer the antibodies for decreased size and access to the tumor site by penetrating the blood-brain barrier. Finally, we will evaluate several candidates for in vivo distribution and the ability to slow tumor cell growth in vitro.
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