SC7: EMERGING TARGETS FOR CANCER IMMUNOTHERAPY
MONDAY, APRIL 8, 2:00 – 5:00 pm

In recent years, the understanding of tumor biology and the many cellular pathways involved has increased significantly. This course will provide some details of how immunology, epigenetics and protein degradation pathways intersect to play a role in tumor development and how they can be exploited to provide new drugs targets for intervention and to enhance the efficacy of current drug treatments. The instructors will review recently published data on immunology (STING, RIG-1), epigenetic (HDAC, HAT), ubiquitin (DUBs, ligases) and autophagy targets and how this knowledge may be used in the development of new standalone or combination therapies for many types of cancers.

Topics to be covered:

• Recent insights and pathways to target the immune system in cancer
• Overview of DUBs and small molecules that target DUBs relevant to immuno-oncology
• Biology of HATs and development of inhibitors of small molecule inhibitors (including PROTACs)
• Relevance of isoform-selective HDAC inhibitors and targeting of repressor complexes
• Review of autophagy pathways and targets that are proving relevant for cancer

Instructors:

Wayne W. Hancock, MD, PhD, Professor of Pathology and Laboratory Medicine, Chief of Transplant Immunology, Children's Hospital of Philadelphia and University of Pennsylvania

Wayne Hancock has more than 400 papers in PubMed, an H-index of 99, and constantly ponders the fine tuning of immune responses, especially with regard to modulation of Foxp3+ T-regulatory cells, but also with regard to effects on conventional T cells. Understanding the nuances of the regulation of key gene sets is likely to boost immune responses and promote durable anti-cancer immunity beyond the current ceiling of ~20% of tumors seen with anti-PD-1 or PD-L1 targeting. While much more needs to be done, there are already clues and data to show how such break-throughs can be achieved by considering the inhibitory effects of Tregs, MDSC, neutrophils and the tumor microenvironment on antitumor immunity.

Aditya Murthy, PhD, Scientist, Cancer Immunology, Genentech, Inc.

Aditya completed his undergraduate and doctoral studies at the University of Toronto, Canada. His PhD explored the role of metalloproteinase enzymes and their inhibitors in inflammation, focusing on cytokine biology. With a growing interest in mucosal immunology, Aditya joined the Immunology Department of Genentech as a post-doctoral fellow in the lab of Dr. Menno van Lookeren Campagne in 2011. Focusing on human genetics and the contribution of germline variants to inflammatory bowel disease, Aditya’s work investigated the role of autophagy, a cellular catabolic process, in regulating the immune response. This work identified a molecular mechanism underlying a common risk variant in the autophagy gene Atg16L1, whereby a missense mutation (T300A) sensitized the protein to Caspase-mediated degradation and compromised autophagy (Murthy et al, Nature 2014). In 2014, Aditya joined the Cancer Immunology department as a Scientist in the stromal biology group led by Dr. Shannon Turley and Dr. Ira Mellman. Currently, Aditya’s group uses insights gained from GWAS (genome-wide association studies) of inflammatory and autoimmune diseases to identify pathways that may contribute to a productive anti-tumor immune response.