Wednesday, April 4 | 6:30-9:00 pm DINNER SHORT COURSE

SC9: Impact of Convergence of Immunotherapy and Epigenetics in Drug Discovery

In recent years, the understanding of tumor epigenetics and immunology have drastically increased. This course will provide some details of how immunology and epigenetic pathways can interact and how they can be exploited to enhance the efficacy of current drug treatments. The instructors will review recently published data on epigenetics target including HDACs, HATs, and DNMTs, the role of the immune system, and how this knowledge may be used in the development of new combination therapies for many types of cancers.

The Effect of DNA Methyltransferase (DNMT) Inhibitors on the Tumor and Host Immune System

Katherine Bakshian Chiappinelli, PhD, Assistant Professor, Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University

• Overview of epigenetic control of innate immune signaling in tumor cells
• Introduction to DNA Methyltransferase inhibitors and their effects on immune parameters
• DNMT inhibitors as anti-cancer agents
• Potential of DNMT inhibitors to sensitize tumors to immunotherapy

Using Selective Histone Deacetylase 6 (HDAC6) Inhibitors to Improve Cancer Immunotherapy

Alejandro Villagra, PhD, Assistant Professor, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University

• New role of HDAC6 as modulators of immune-related pathways
• Molecular mechanisms controlling the expression of PD-L1 and other immunosuppressive pathways
• Use of selective HDAC inhibitors as adjuvant in immunotherapy
• Combination of HDAC6 inhibitors and immune check-point blockade; rationale and in vivo consequences

Histone Acetyl Transferase (HAT), HDAC and Nuclear Repressor Complex Targeting to Promote Adaptive Immunity in Cancer

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

• Overview of epigenetic regulation of host immune cells
• HDAC and HAT targeting of T cell subsets in syngeneic tumor models
• Optimal combinatorial strategies to promote antitumor immunity

Instructor Bios

Katherine Bakshian Chiappinelli, PhD, Assistant Professor, Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University Cancer Center

Katherine Bakshian Chiappinelli joined the GW Department of Microbiology, Immunology and Tropical Medicine in 2017 as an Assistant Professor. Dr. Chiappinelli received her PhD in Developmental, Regenerative, and Stem Cell Biology 
from Washington University in St. Louis under the supervision of Dr. Paul Goodfellow in 2012. Dr. Chiappinelli pursued postdoctoral studies at Johns Hopkins University with Dr. Stephen Baylin investigating the epigenetic control of immune signaling in cancer cells. Her research focuses on how epigenetic therapies can be used against cancers, specifically in the context of arming the host immune system to fight cancer cells.

Alejandro Villagra, PhD, Assistant Professor, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University

Alejandro Villagra’s research in “immunoepigenetics”, the combination of epigenetics and immunotherapy, focuses on training the immune system to kill invading cancer cells and tumors. This method of treatment, which would reduce the dependency on radiation and chemotherapy, involves disrupting the pathways that allow tumors to “trick” the immune system and grow and travel throughout the body. He and his team hope this work will lead to new drugs and therapies that will ultimately strengthen the immune system and allow it to recognize and attack cancer cells more effectively.

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

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 (and it won’t be by doing more of the same).