Targeting the suppressors.
Brian Brown, PhD
Icahn School of Medicine at Mount Sinai
“It’s not always appreciated how much science has improved the treatment of cancer but there have been many incredible advances over the past few years that have led to long-lasting patient remissions. This has come from major innovations, including in gene and cell therapy, that enabled us to harness a patient’s immune system to attack cancer. I believe we are just at the beginning of this revolution in cancer treatment,” says Brian Brown, PhD, professor and associate director of the Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai (New York, NY).
Dr. Brown has been inspired by the potential of cell and gene therapies for more than 20 years. Now, with funding from Alliance for Cancer Gene Therapy, Dr. Brown and his team in the Brown Lab are working toward a potential breakthrough in the fight against solid tumors.
Despite some amazing successes, not all patients respond to current immunotherapies. Dr. Brown notes that one cell type that appears to be responsible for poor responses to immunotherapy against solid tumors is called a macrophage. As part of the natural immune system, macrophages typically protect patients from infections, but tumors can reprogram macrophages to suppress other immune system cells and keep them from killing cancer cells. It’s this behavior that Dr. Brown intends to stop by equipping a patient’s own T cells to kill immune-suppressing macrophages in tumors.
Dr. Brown’s creative strategy is rooted in the success achieved by chimeric antigen receptor (CAR) T-cell therapy, which engineers T cells to target and kill cancer cells.
“Solid tumors are full of immunosuppressive macrophages,” says Dr. Brown, “and these macrophages can keep T cells from entering the tumor or killing the cancer cells, even when we give drugs that invigorate the T cells.
“Our goal is to develop a new CAR that specifically kills macrophages in tumors while sparing macrophages in healthy tissue. Doing this will clear the way for other T cells to enter and destroy the tumors.
“What makes this particularly exciting is that immune-suppressive macrophages are common to many types of tumors, so even though our research targets lung cancer, our approach may be effective in treating many different types of cancers.
“I believe gene and cell therapies have the potential to revolutionize medicine. For many years I had to defend this opinion from critics who didn’t believe it would ever work. Now the success speaks for itself. Children born with devastating genetic diseases and leukemia patients of all ages are seeing their disease effectively treated with gene and cell therapies.”
“These successes demonstrate the power of innovative thinking and the tenacity of scientists to translate ideas into solutions. Early failures provided valuable insights that are making it possible to find successful ways forward. We are grateful for risk-taking organizations like Alliance for Cancer Gene Therapy that are willing to fund new ideas even when clinical success is not necessarily assured.”