Cell Design Labs

Cell Design Labs is a biotechnology developing cell-based therapies based on innovative research from Dr. Wendell Lim's lab at UC San Francisco. Using its patented technology platform for custom cell engineering, Cell Design Labs aims to develop anticancer therapies and also create partnerships with leading oncology companies. The company is initially focused on cancer, including both hematologic and solid tumors but the technology may also have applications in autoimmune and degenerative disorders.

The company's preclinical product candidates, including therapies for prostate cancer and hepatocellular carcinoma that use their synNotch technology and the lead preclinical candidate which targets multiple myeloma.

Cell Design Labs uses their synNotch technology, to rewire immune cells and create customized cells that can carry out highly specialized actions in the body. Their system has anticancer applications, since T cells engineered with synNotch receptors could be programmed to produce and deliver a therapeutic payloads to tumor sites, such as checkpoint inhibitors, bispecific antibodies and custom cytokines. The company aims to use synNotch technology to generate more effective and safer therapeutics for cancer, autoimmune and infectious diseases.

In 2017, Gilead Sciences and its subsidiary Kite Pharma agreed to acquire Cell Design Labs for up to approximately $567 million. synNotch technology is being applied to treat autoimmune diseases in a collaboration between Gilead, Kite and Kyverna Therapeutics.

SynNotch is a synthetic Notch receptor. Notch is a well-characterized receptor found in all multicellular organisms and discovered in 1914. Notch functions in cell communication with both external and internal functionality. The Notch receptor outside the cell binds a molecular partner in a neighboring cell. This interaction causes the Notch receptor to be physically linked with the neighbor cell and allows the internal portion of Notch to move into the nucleus where it activates various genes.

A programmable immune cell is created by expressing synNotch in T cells. The synNotch receptor conveys sensor functionality to T cells, which naturally roam throughout the body to find targets. After a reprogrammed cell binds to its intended target (i.e., a cancer cell), it can trigger specific molecular activities such as producing anticancer defenses .

The SynNotch system is also being used in another synthetic biology application, the generation of self-organizing tissue. At UCSF, Lim’s lab used synNotch to program two groups of cells to self-organize into a two-layered sphere. One group of cells expressed a signaling protein on their surfaces and the second group were engineered with a custom synNotch receptor programmed to detect the protein on the surface of the other cells. Neither of the cell types formed structures on their own but when grown together, the first cells activated the other cells to produce cadherin proteins, making them sticky and cluster together. The sticky cells formed a core and the other cells formed the outer layer. In the paper published in Science in 2018, Lim’s group demonstrated self-assembly of multiple tissue patterns and the ability of their spheroids to self-repair when damaged.