New Finding of Responses to CTLA4 Blockade in Metastatic Melanoma

Cancer immunotherapy is quite popular in recent years. From the beginning of the discoveries that our immune system can inhibit cancer growth, along with the multiple roles of the immunologic mechanism in cancer cells to the current clinical trials, there are indeed a lot of debates about cancer immunotherapy, as well as continuous scientific results.

In various treatment methods, CTLA4 related methods attracts considerable attention. CTLA4 is a molecule expressed on the surface of T cells that can blocking their proliferation. CTLA-4-blocking antibody drug, which stimulates T-cell response,  can target the cancer cells and significantly prolong the survival of many melanoma patients. But not all patients respond to this treatment: some patients can survive for many years, while some other patients did not react. What is the cause of this, however, has been uncertain in the field of cancer research.

In the latest journal Science, researchers of Dana-Farber Cancer Institute, the United States, found that a number of metastatic melanoma patients treated by a new cancer immunotherapy produced different tumor antigens. This finding indicates that the targeting molecular of immunotherapy may vary with different individuals, which means the future projections of immunotherapy therapeutic effect on the patients will be more difficult.

This new treatment used a drug called ipilimumab, “a monoclonal antibody that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.”—wiki. The ipilimumab (trade name Yervoy) was approved for the treatment of advanced melanoma by US FDA on March 25, 2011.

This is a relatively new method of treating cancer - immune checkpoint inhibitors, which can help reactivate tumor immunity, thereby opening the body's natural barrier to kill cancer cells.

Previous small studies have shown good efficacy in patients with ipilimumab therapy, as their tumors appeared multiple mutations that produced large amount of new antigen protein that the immune system attacked. The latest large-scale experiments, with tumor tissue analysis of more than one hundred patients, found a large number of cancer patients who had "new antigen (neoantigen)", are those having the best efficacy with ipilimumab therapy.

In another related article published on July’s Science, researchers from National Institute of Allergy and Infectious Diseases, knocked a gene called LRBA in T cells and found CTLA4 protein levels drop dramatically. Thus researchers suggested that for patients with LRBA mutations the CTLA4 therapy may be more effective, which will also contribute to more in-depth exploration of the molecular mechanisms of cancer immunotherapy.