Production of T cells using engineered soluble DLL4 ligands
Background
Chimeric Antigen Receptor T-cell (CAR T-cell) therapies are a therapeutic tool for the treatment of several types of cancers, most notably lymphomas and leukemia. Healthy T cells are taken from the patient’s blood, cultured in the laboratory to induce differentiation, and ingenerated by adding a chimeric antigen receptor (CAR). After modification, the CAR T-cells are then reinjected into the patient's bloodstream. The presence of CAR allows the engineered T cells to specifically recognize and target cancer antigens. While promising, CAR T-cell therapy remains prohibitively expensive, as it relies on a culture system known as plate-bound DLL4. Plate-bound DLL4 methods have limitations as a limited number of cells can be successfully cultured and differentiated due to the small surface area of tissue-culture plates, which can make large-scale production challenging and time-consuming.
Technology Overview
Researchers at Boston Children’s Hospital have developed an innovative method using soluble DLL4 to culture T-cells in suspension rather than in a plate-bound system. The team has developed several oligomeric states of DDL4 that, similarly to the plate-bound method, allows T-cell culture and differentiation by the Notch pathway, without the use of plates. This method allows for culturing high amounts of cells in suspension, in a faster and more economical fashion.
Applications
- Increased efficiency of CAR T use in current therapies
- Potential use for the production of other immune cell lines such as NK and HSC
- Possible industrial applications for scale-up productions
Advantages
- Faster culturing of immune cells for CAR T-cell therapy
- Decreased costs associated with maintaining and differentiating T cells
Patents
- PCT Pending WO 2024/076499
