Development of a Trifunctional Self-Renewing Memory CAR T Cell Therapy to Overcome the Heterogeneity and Suppressive Microenvironment of Glioblastoma
Grant Award Details
Grant Type:
Grant Number:
DISC2-16638
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$2,700,810
Status:
Active
Grant Application Details
Application Title:
Development of a Trifunctional Self-Renewing Memory CAR T Cell Therapy to Overcome the Heterogeneity and Suppressive Microenvironment of Glioblastoma
Public Abstract:
Research Objective
This personalized chimeric antigen receptor (CAR) T cell therapy will attack a wider range of cancer cells, and block cancer's defense mechanisms to empower the immune system to better fight cancer.
Impact
This CAR T cell therapy will help patients with glioblastoma (GBM) and other high-grade gliomas, and it will advance the immune cell therapy field as a whole to treat solid tumors more effectively.
Major Proposed Activities
This personalized chimeric antigen receptor (CAR) T cell therapy will attack a wider range of cancer cells, and block cancer's defense mechanisms to empower the immune system to better fight cancer.
Impact
This CAR T cell therapy will help patients with glioblastoma (GBM) and other high-grade gliomas, and it will advance the immune cell therapy field as a whole to treat solid tumors more effectively.
Major Proposed Activities
- Develop a bispecific CAR that binds two different targets on tumor cells. This activity will test for anti-tumor function in several diverse glioma models both in vitro and in vivo.
- Compare several approaches to multi-target CAR function, including pooling different CAR T cells, engineering CAR T cells to express two different CARs, or designing one CAR that binds to two targets.
- Generate and optimize the anti-SPP1 blocking antibody (antigen binding portion, scFv) to be included in the human CAR T cell therapy. The anti-SPP1 will be secreted into the tumor microenvironment.
- Evaluate in mice the anti-SPP1-secreting CAR T cells and compare to previous data of injecting anti-SPP1 systemically, which showed successful blocking of immunosuppressive tumor elements.
- Optimize the CAR T cell therapeutic candidate that includes a bispecific CAR that targets two different tumor antigens and a secreted anti-SPP1 to block the immune-hostile tumor microenvironment.
- Evaluate the CAR T cell therapeutic candidate in human GBM spheroid- and organoid-microglia models to support evaluation for the upcoming clinical trial.
Statement of Benefit to California:
Developing cellular immunotherapy both advances medical science and fosters local innovation, creating jobs and bolstering the state's reputation as a leader in cutting-edge healthcare. Through CIRM, California has pioneered cutting-edge immunotherapy treatments, maintaining its position as a global leader in biotech innovation, while providing hope and improved outcomes for patients statewide and across the world.
