Discoidin Domain Receptor 1 (DDR1)

Class

Humanized IgG1 monoclonal antibody (blocks DDR1-collagen interaction)

Pathway

Tumor stromal collagen alignment / reversal of immune exclusion

Discoidin Domain Receptor 1 (DDR1) is a receptor tyrosine kinase, a cell-surface protein that transmits signals into the cell after binding a specific molecule outside it. Unlike most receptor tyrosine kinases, which respond to growth factors, DDR1 is activated by collagen, the structural protein that forms much of the connective tissue scaffold in organs and tumors. In many solid tumors, DDR1 signaling promotes the deposition and alignment of collagen fibers into dense, organized bundles around cancer cells. This altered extracellular matrix acts as a physical and biochemical barrier that limits the infiltration of immune cells, particularly T cells, into the tumor core, a phenomenon known as immune exclusion. Blocking DDR1 with a monoclonal antibody that prevents collagen from engaging the receptor aims to disrupt this collagen architecture, potentially restoring T cell access to tumor tissue. This mechanism is of broad interest in oncology, especially in cancers characterized by dense fibrotic stroma, and is often considered in combination with immunotherapies whose efficacy depends on immune cell infiltration. Beyond oncology, DDR1 also participates in tissue remodeling and fibrosis in organs such as the kidney and lung, making it a target of interest across fibrotic disease more generally.