Funded Grants

SEED GRANT

Grantee: City of Hope
Project Lead: Darya Alizadeh, PHD
Grant Title: Advancing IL13Ra2-CAR T cell Therapy against Glioblastoma by Enhancing IFN-Signaling
Program Area: Glioblastoma
Grant Type: UKF Seed Grant
Year Awarded: 2023
Amount: $50,000
Duration: 1 year

Summary: Glioblastoma (GBM) - the most common and aggressive form of brain cancer- is among the deadliest cancers affecting adults and children. The average length of survival for GBM patients is estimated to be only 8 months. Despite aggressive standard-of-care therapies, tumor recurrence is almost inevitable and uniformly lethal. Survival rates and mortality statistics for GBM have been virtually unchanged for decades.

Given the current dearth of effective therapeutic options for these patients and the modest effects of various immunotherapies evaluated to date, it is of critical urgency to identify novel strategies for future clinical evaluation. Cancer immunotherapy has revolutionized treatment options for many solid tumors, including brain cancers. Chimeric Antigen Receptor (CAR) T cells, a form of cellular immunotherapy, are a type of immune cells engineered with a synthetic receptor to recognize cancer cells. CAR T cell therapy has shown tremendous impact in hematological cancers but have faced some challenges in solid tumors. One of the challenges in CAR T cell therapy of solid tumors, such as GBM, is the suppressive tumor environment, which prevents both CAR T cells and patient’s immune cells from recognizing the tumor. However, one immune cell type (myeloid cells), is found abundantly in brain tumors. We have previously shown that the immune stimulating factor (IFNγ) secreted by activated CAR T cells has the ability to potently change myeloid cell function to become anti-tumor immune cells.

This proposal aims to improve CAR T cell therapy for brain tumors by engineering our CAR T cells to enhance IFNγ signaling, which will not only promote CAR T anti-tumor function but increase their ability to reprogram resident myeloid cells against the tumor. Our preliminary studies have shown that this approach is promising and feasible. This approach will condition glioma tumors to be more susceptible not only to CAR T therapy, but other treatment options that could increase the overall survival of patients. Lastly, the success of this proposal will also generate a technology platform for the treatment of other challenging cancers that lack effective treatment options.