Human iPSC-derived chimeric antigen receptor expressing macrophages for improved cancer treatment.
Grant Award Details
Grant Type:
Grant Number:
DISC2-12657
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$1,256,332
Status:
Active
Progress Reports
Reporting Period:
Year 2
Grant Application Details
Application Title:
Human iPSC-derived chimeric antigen receptor expressing macrophages for improved cancer treatment.
Public Abstract:
Research Objective
These studies will produce a new CAR-targeted iPSC-derived macrophage-based cell therapy product for treatment of refractory malignancies such as ovarian cancer.
Impact
These studies eliminate a bottleneck in macrophage production and enable these cells to be engineered and manufactured in a standardized, off-the-shelf manner, rather than on a patient-specific basis.
Major Proposed Activities
These studies will produce a new CAR-targeted iPSC-derived macrophage-based cell therapy product for treatment of refractory malignancies such as ovarian cancer.
Impact
These studies eliminate a bottleneck in macrophage production and enable these cells to be engineered and manufactured in a standardized, off-the-shelf manner, rather than on a patient-specific basis.
Major Proposed Activities
- Generate of human iPSCs with stable expression of tumor antigen-targeted chimeric antigen receptor constructs
- Generate and evaluate in vitro anti-cancer activity of human iPSC-derived CAR-expressing macrophages (human iPSC-CARMAs) with different intracellular signaling modalities
- Demonstrate efficacy of human iPSC-CARMAs against ovarian cancer in vivo
- Improve efficacy of human iPSC-CARMAs in vitro and in vivo by combination with additional immune stimulating agents agents
- Enable large-scale expansion of iPSC-CARMACs via autonomous cytokine expression.
- Improved cryopreservation of iPSC-CARMACs
Statement of Benefit to California:
Over 2500 women per year in California are diagnosed with ovarian cancer, and the majority of these women will die of their disease. If this cancer is not cured at an early stage, the disease will almost inevitably relapse. Therefore, new and better treatments are desperately needed. This project to use human iPSC-derived macrophages for a targeted cancer treatment provides a completely new strategy for better treatment and cure of ovarian cancer and other refractory malignancies.