Researchers will evaluate whether a new immune-based therapy for an incurable brain tumor that primarily occurs in children can be developed and effectively used in an animal model that resembles human cancers.
A lethal brain tumor, diffuse interstitial pontine glioma, occurs primarily in children. It is resistant to all currently marketed therapies and cannot be surgically removed because it is diffusely located within areas of the brainstem that are critical for maintaining life. One somewhat promising experimental approach to therapy involves using monoclonal antibodies to target a molecule, called “epidermal growth factor receptor” (EGFR) that resides on the surface of the glioma cells. Clinical trials of a monoclonal antibody, Nimotuzumab, which targets this receptor has demonstrated some therapeutic benefit in children with recurrent glioma, but was not curative. The investigators at MDACC, therefore, will explore whether this monoclonal antibody can be used to fashion T cells, a type of immune cell, so that they can be made into a weapon to fight this brain cancer. To explore this possibility, they will undertake research as part of an experimental therapeutic approach that is being tested in pet dogs suffering from a similar spontaneous brain tumor.
T cells have a native ability to kill cancer cells upon contact. Each T cell has a specialized receptor that is targeted to a specific protein on other cells, such that different T cells can sometimes target different tumors. The problem in developing T-cell therapy for pontine glioma is that naturally-ocurring T cells in children are unfortunately not capable of recognizing the glioma tumor cells. The investigators have developed a new technology to circumvent this problem by introducing into to T cells some of the genes that code for the Nimotuzumab monoclonal antibody coupled to areas of activity that can make a modified T cell specifically target EGFR, the receptor located on the glioma cells. They first will see whether this new technique effectively targets the similar brain tumors in the pet dogs. Through a collaboration with scientists at Texas A and M University, they have arranged for the pet dogs with spontaneously-occurring gliomas to receive their own T cells that have been engineered to specifically target canine EGFR on the glioma cells. Success would pave the experimental use of this technique in children with diffuse interstitial pontine glioma.
Significance: This new technique for engineering immune T cells to specifically target deadly diffuse interstitial pontine glioma cancer in children that may ultimately lead to a cure.