Description:
Abstract
USC researchers have developed a technique for optimizing CAR-T and CAR-NK cell specificity that employs human leukocyte antigen DR (HLA-DR) downregulation in malignant cells. Because malignant cancer cells generally express HLA-DR at lower levels than healthy cells, CAR-NK cells inhibited against HLA-DR will preferentially target malignant cancer cells, reducing the chance of on-target off-tumor toxicity.
Benefit
- Improves specificity of CAR-T and CAR-NK cells against hematologic malignancies
- Reduces likelihood of on-target off-tumor toxicity
- Technique could be adapted to target solid tumors
Market Application
T cells and natural killer (NK) cells engineered with chimeric antigen receptors (CAR) offer a promising new treatment option for cancer, especially hematologic malignancies. However, target antigens are often expressed on both cancerous and noncancerous cells, meaning that CAR-T and CAR-NK cells can erroneously attack healthy cells — a severe side effect called on-target off-tumor toxicity. Thus, new methods to improve CAR-T and CAR-NK cell specificity against cancer are needed.
Publications
Targeting HLA-DR loss in hematologic malignancies with an inhibitory chimeric antigen receptor, Fei et al., 2022.
Other
Stage of Development
- Tested in vitro
- Tested in vivo in xenograft mouse model
- Available for exclusive license
IP Status
US Patent pending