The Immuno-Oncology Revolution
Why Do So Few Patients Respond To Checkpoint Inhibitors?
How Can We Improve Patient Response To Checkpoint Inhibitors?
Delivering on the Promise of Immunotherapy Using CMP-001
Checkmate Pharmaceuticals is pioneering new therapies to allow more patients living with cancer to benefit from immunotherapy treatments. Our lead clinical candidate, CMP-001, is a differentiated and potent activator of Toll-like Receptor 9 (TLR9) found in tumor infiltrating plasmacytoid dendritic cells (pDC)—commonly known as “the bad actors” of the immune system.
Immature pDCs are recruited by tumor cells to maintain an immune suppressed tumor microenvironment. This weakens the body’s defenses against cancer by preventing the immune system from recognizing and attacking unhealthy tumor cells. Clinical studies across various solid tumors demonstrate the ability of CMP-001 to safely and selectively activate the innate immune system and manipulate the tumor microenvironment, ultimately unleashing the body’s natural defenses to fight cancer.
A closer look at CMP-001 and its role turning “cold” tumors “hot”
CMP-001 works by activating TLR9 (the receptor for CpG-A) in plasmacytoid dendritic cells (pDC). pDCs are the only immune cells that produce large quantities of type I interferons (IFNα and others). When activated, pDCs increase their expression of important co-stimulatory molecules and tumor antigen presentation to T cells, culminating in the generation of effective anti-tumor T cell responses.
A tumor is immunologically cold when immature pDCs are recruited by the tumor to maintain an immune-suppressed tumor microenvironment (TME). Immune-suppressing regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC) are supported by immature tumor-infiltrating pDC which do not produce type I IFNα.
CMP-001 activates immature pDCs through TLR9, releasing high concentrations of type I IFNα, along with a complex mixture of Th1-promoting cytokines and chemokines. This release of immune agents into the tumor and draining lymph nodes “resets” the TME making the cancer “hot”. pDC activation suppresses Treg and MDSC, attracts and activates other DCs and anti-tumor T cells into the tumor, and results in local and systemic tumor regression.