T cells, a type of immune cell, can prevent and treat malignancies. This project seeks to harness the therapeutic potential of T cells from the patient to treat diffuse intrinsic pontine glioma (DIPG). This devastating brain tumor occurs in young children and is unfortunately untreatable despite the application of chemotherapy and radiation. Immunotherapy offers a new approach as T cells can be fashioned outside the body to have desired specificity and thus administered as an investigational therapy. Indeed, we are currently infusing T cells that have been engineered to express a chimeric antigen receptor (CAR) that targets the molecule CD19 present on leukemias and lymphomas arising from malignant B cells.
In this project we seek to build upon these clinical trials to genetically modify T cells to target DIPG. This will be accomplished by recognizing and overcoming several major challenges. Namely, that one CAR molecule will not target all DIPG, thus T cells expressing multiple CARs will be generated and tested. In addition, the design of the CAR will impact the ability of the engineered T cell to eradicate tumor cells, thus we have developed an approach to screen a large panel of CAR molecules. Lastly, we will temporarily express the CARs to limit the possibility that the infused T cells will inadvertently recognize normal structures. In aggregate, this project seeks to innovate a new approach to generate large numbers of CAR molecules and provides a pathway to selecting which genetically modified T cells might have potency for DIPG.