Cancers Evade Immunotherapy by “Discarding the Evidence” of Tumor-Specific Mutations, Hopkins Study Shows; Findings Could Explain Widespread Acquired Resistance Among Patients Treated with Immune Checkpoint Blockade Drugs

Results of an initial study of tumors from patients with lung cancer or head and neck cancer suggest that the widespread acquired resistance to immunotherapy drugs known as checkpoint inhibitors may be due to the elimination of certain genetic mutations needed to enable the immune system to recognize and attack malignant cells. The study, conducted by researchers on the cells of five of their patients treated at the Johns Hopkins Kimmel Cancer Center, is described in an article published online on December 28, 2016 in Cancer Discovery. The article is titled “Evolution of Neoantigen Landscape During Immune Checkpoint Blockade in Non-Small Cell Lung Cancer.” "Checkpoint inhibitors are one of the most exciting recent advances for cancers, but the mechanism by which most patients become resistant to these therapies has been a mystery," says Victor E. Velculescu (photo), M.D., Ph.D., Program Leader in the Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins and Professor of Oncology. Clinical trials with the drugs to date have shown that nearly half of patients with lung cancers eventually develop resistance to this class of drugs for reasons that have been unclear. Checkpoint inhibitors, such as nivolumab and ipilimumab, approved by the FDA for use against lung cancer, metastatic melanoma, head and neck cancer, and Hodgkin lymphoma, help the immune system recognize cancer cells by revealing evidence of mutated proteins called neoantigens on the surface of cancer cells. To investigate why checkpoint inhibitors so often stop working, Dr. Velculescu; Valsamo Anagnostou, M.D., Ph.D., Instructor of Oncology at the Johns Hopkins University School of Medicine; Kellie N.
Login Or Register To Read Full Story