Mechanism of Action
In Hot Pursuit to Solve Immunotherapy’s Biggest Challenge
Converting Immunologically “Cold” Tumors to “Hot”
Recent advances in cancer immunotherapy are providing new treatment options and better outcomes for people living with cancer. Immunotherapy treatments, such as immune checkpoint inhibitors, work by releasing the brakes on the immune system and allowing special immune cells, known as T cells, to produce a self-sustaining attack on a tumor. However, checkpoint inhibitors are generally only effective in hot tumors which contain T cells. Most people living with cancer have cold tumors, without T cells, and do not respond to this immunotherapy.
Checkmate Pharmaceuticals’ mission is to tackle one of the greatest challenges for physicians and patients in cancer immunotherapy: converting immunologically cold tumors to hot. The unique mechanism of action of our lead compound, CMP-001, along with its delivery as a Virus-like Particle, or VLP, has been shown to reverse cold tumors, making them “hot” or susceptible to immunotherapy treatment with checkpoint inhibitors.
CMP-001 initiates local and systemic immune responses to fight cancer, potentially improving outcomes for people whose tumors are non-responsive to immunotherapies. CMP-001 is being investigated in patients with various types of cancer, including melanoma, lung, and head and neck, whose tumors have proven to be resistant to checkpoint inhibitors. It is also under investigation for certain types of cancer that are particularly resistant to immunotherapy, such as colorectal cancer.
Making Immunotherapy Work Harder
For decades, it has been known that certain immune cells called cytotoxic T lymphocytes (CTLs) can destroy cancer cells, yet they fail to play this key role in many patients suffering from cancer. Tumors produce “immune checkpoint proteins” that suppress the cancer fighting activity of CTLs. This discovery led to a new class of therapeutics called checkpoint inhibitors. While these therapies are a significant advance, they fail to work on many types of cancer.
The efficacy of checkpoint inhibitors may be dramatically increased by combining them with an immune activator to stimulate T cells. Many different immune activators have been tested and the Toll-like receptor 9 (TLR9) agonist CpG-A oligonucleotides, like CMP-001, have been found to be the strongest at stimulating anti-tumor CTLs. The unique combination CMP-001 with checkpoint inhibitor therapy may result in increased clinical benefit and provide new treatment options for patients with cancer.