TECHNOLOGY

Zonula's novel small molecules targeting cell adhesion represent a new approach to treating fibrosis dependent diseases.

Cell adhesion, or how cells stick to one another, is a fundamental biological property. Our molecules bind to proteins, known as cadherins, on the cell surface. These proteins promote cell adhesion by interacting with one another. Zonula's molecules prevent cell adhesion by binding to a surface protein called N-cadherin (see below diagram). Zonula’s small molecules can modulate many biological processes, one of which being fibroblast adhesion and secretion of collagen. When cell adhesion is manipulated, a wide variety of diseases can be treated.

N-cadherin inhibitors enable immunotherapy

The immune system can kill cancer cells, but tumors (such as pancreatic tumors) manage to evade attack by forming an immuno-protective barrier. This barrier is made of cells called cancer associated fibroblasts (CAFs). There is a need to disrupt the immuno-protective barrier surrounding cancer cells to enable immunotherapy using either the body’s own immune system or cellular therapies such as genetically engineered chimeric antigen receptor (CAR) T cells. 

CAFs stick together using N-cadherin on their surface and produce a thick material called collagen which blocks access of T cells to the cancer cells. N-cadherin inhibitors can be used to attack the CAFs which form the barrier. Inhibitors of N-cadherin block CAF adhesion and collagen production. These inhibitors may allow T cells to penetrate the tumor. The idea that N-cadherin inhibitors can be used to lower the CAF barrier, thereby facilitating immunotherapy is currently being explored by Zonula.