UAB Comprehensive Cancer Center Magazine Spring 2017 - Page 6

and Cancer Center senior scientist. Much of this work is find ways to control that degree of exhaustion and/or extend conducted through the center’s Inflammation, Immunology the time that activation is maintained, which would allow and Immunotherapeutics Research Program, which Dr. for a better immune response. Buchsbaum co-leads with senior scientist Troy Randall, The BCRFA has also awarded a grant to Dr. Ph.D. Buchsbaum and Sara Cooper, Ph.D., with the One such project involves patients with triple negative HudsonAlpha Institute for Biotechnology in Huntsville, breast cancer, a particularly aggressive and difficult-to-treat to investigate what is referred to as the immune repertoire, form of the disease. An earlier clinical trial conducted at the the number of different sub-types of T cells made by the Cancer Center and led by senior scientist Andres Forero, immune system. In this study, the Cancer Center provides M.D., and Cancer Center director emeritus Albert LoBuglio, HudsonAlpha tumor samples, and through genomic testing, M.D., examined triple negative breast cancer patients who they identify the number of T cell clones within that tumor. responded to therapy versus those who did not. Through Researchers at HudsonAlpha have shown that in animal genomic analysis of tumor specimens, they discovered that models, after transfecting (or inserting) a transcription patients who responded to treatment expressed MHC II factor into the tumor model, there was no difference in the genes, which are associated with immune activation, and distribution of T cell clones in the animal that was immune the non-response patients did not. responsive to the tumor versus not. With funding support from the Researchers did see, however, a “The concept of using Breast Cancer Research Foundation large increase in the size of the T cell immunotherapy dates as of Alabama (BCRFA), that work clones within the responsive tumor has been and continues to be studied compared to the non-responsive. The far back as the late 1800s. in animal models to develop new significance of this finding is that It’s incredibly exciting that a techniques for future clinical trials. it potentially allows for monitoring century-plus later we have “In certain breast cancer animal immune activation in a real-time models, we have found that the use of basis. real evidence that we can HDAC inhibitor can upregulate the “If these activated T cells are put into practice.” transcription factors associated with present in one patient and not the MHC II pathway,” Dr. Buchsbaum another, then you know to continue Donald Buchsbaum, Ph.D., says. “Our intent is to study that in to treat the patient whose immune professor and direc tor of the UAB combination with checkpoint inhibitor system is being activated and try a Division of Radiation Biology and antibody therapy and to use other different approach in the other,” Dr. Cancer Center senior scientist procedures to further enhance that Buchsbaum says. “There is no benefit response.” from a patient not responding and just At the same time, the Cancer Center is also involved in waiting to see if they do. If we can measure the size of the a clinical trial examining HDAC inhibitor in combination clones of active T cells, then we have a way to monitor the with checkpoint inhibitor antibody therapy for triple activation of the T cells. Currently, we don’t know how to negative breast cancer patients. “We’re studying in parallel gauge the level of response. We need real-time monitoring, in the laboratory as well as clinical trials this approach and this approach allows us to do that.” to enhancement of immune activation and response,” Dr. Immunotherapy research also plays a role in Buchsbaum says. This work is a collaboration among him, understanding cancer metastasis, says Lalita Shevde- Drs. Randall and Forero, as well as Mei Li, Ph.D., and Samant, Ph.D., professor in the UAB Department of M.D.-Ph.D. student Tyler McCaw. Pathology and Cancer Center senior scientist (see Scientist Another promising project, which is being led by Profile, page 21). Dr. Samant is currently investigating Dr. Randall, is examining the phenomenon of T cell the cross-talk between breast cancer cells and cells of the exhaustion. Studies in some animal models have shown that innate immune system known as macrophages. Cancer cells when MHC II expression is increased, there is a period of tend to reprogram and polarize these macrophages and tumor regression, followed by tumor regrowth – meaning make them allies by fostering tumor growth. Dr. Samant’s that the activated immune cells are becoming exhausted and laboratory is investigating how morphogens from the no longer effective. Dr. Randall and his team are trying to hedgehog signaling pathway communicate from the breast 4 U A B C O M P R E H E N S I V E C A N C E R C E N T E R