For patients suffering from relapsed/refractory ALL or other B-cell malignancies, CAR T-cell therapies may give doctors who have exhausted traditional chemotherapies another tool to use. Michael Bishop, MD, professor of medicine, is lead- ing CAR T-cell trials at the University of Chicago and has seen promising patient outcomes (see sidebar below). Collaborative and transdisciplinary research efforts are helping elevate immunotherapies to a new level. Wenbin Lin, PhD, James Franck Professor of Chemistry, and colleagues including Weichselbaum are making checkpoint inhibitor immunotherapies more effective through the use of photodynamic therapy (PDT), a treatment that uses a drug called a photosensitizer. When photosensitizers are exposed to a specific wavelength of light, they produce a lethal type of oxygen that can kill cancer cells. Gajewski and Luke will lead a phase II study that examines how changing a person’s gut bacteria can impact the efficacy of pembrolizumab in melanoma. Still in early stages, the trial will be supported by Evelo Biosciences, a leading immune-microbiome company. In addition, basic science researchers are working to understand the basic wiring of the immune system, laying the groundwork for the develop- ment of future cancer therapies. Investigators like Hans Schreiber, MD, PhD, professor of pathology, and Peter Savage, PhD, associate professor of pathology, are leading their fields in cancer immunology. These are just a few examples of how our research- ers’ innovative and targeted approaches are shap- ing the future of immunotherapy, ensuring more effective treatments and better patient outcomes. 1 Gajewski, Mol Oncol 6:242-250, 2012. 2 Gajewski et al., Immunol Rev 213:131-145, 2006. 3 Gajewski et al., Semin Oncol 42:663-671, 2015. 4 Zheng et al., Oncotarget 7:43039-43051, 2016. 5 https://clinicaltrials.gov/ct2/show/record/ NCT02608385 CAR T-Cell Therapy Offers Patient Hope While driving the 500 miles from a client in Ten­ nessee to his home in Michigan, Andy Parker, 59, a tool and die engineer, noticed that his lower leg was sore and swollen. He thought it might just be how he was sitting. But, an ultrasound scan revealed three blood clots in that leg and a lethal disease—acute lymphoblastic leukemia (ALL). Parker immediately began chemotherapy. After one round of treatment: no change. Second round: no change. After unsuccessful treatment at a second institution, Parker was referred to Michael Bishop, MD, professor of medicine and an expert in CAR T-cell therapy, at the University of Chicago Medicine. “Dr. Bishop had something new,” Parker recalled. “I decided to do it. I had no choice.” In Chicago, Bishop collected some of Parker’s T cells. He sent them to KITE Pharma, a California lab where they inserted proteins that enable T cells to detect and destroy the errant cells. Then they sent vast numbers of those T cells back. But before the T cells arrived, the FDA shut down the trial. Bishop immediately went to bat for Parker. Two weeks later, the FDA allowed treatment on a compassionate-use basis. The treatment began with an IV drip, but instead of drugs, in flowed a few million search-and-destroy T cells, trained to wipe out the misguided leukemic cells. This time, tests showed no leukemia, no sign of cancer. One month later, a second test confirmed: no cancer. Parker is now back at work, nearly back to normal, and plans to get married in the spring. CANCER.UCHICAGO.EDU 5