Targeting NF1 Mutant Glioma Oncoproteins with Peptide Centric CAR T Cells

NF1 patients sometimes develop high grade glioma (HGG), a malignant brain tumor. Currently, there is no effective therapy against this devastating tumor, even though efforts continue to develop drugs that specifically eliminate these tumors. 

Our bodies have a very efficient system, our immune system, to deal with abnormal cells (for example virus infected cells). Unfortunately, most tumor cells are not recognized by our bodies as abnormal, and tumors can thus hide from the immune system and specifically our T-cells. In recent years, CAR-T therapy has been developed which has been successful in treating a number of cancers. In CAR-T therapy, we take T-cells from the blood of a patient, “teach” them in the lab to recognize and kill the tumor and give them back to the patient. These T-cells will go after the tumor and eliminate it. It is of utmost importance to teach the T-cells to recognize something that is unique to the tumor (tumor antigens) and not present on any normal cells, because otherwise our immune system will start attacking normal healthy cells. It has proven very challenging to identify these unique tumor antigen targets. This study takes a novel approach to identify unique tumor antigens. Crucially, this approach has already been successful in developing CAR-T therapy for neuroblastoma (a common childhood cancer) and the first clinical trials with this therapy are slated to begin enrollment in early 2023. 

The goal is to repeat the neuroblastoma success story in NF1 associated gliomas, to have identified a unique tumor antigen and to have performed all the studies needed to convince the FDA to start an NF1 centric CAR-T therapy clinical trial within a year following the completion of this study.