New federal funding supports work led by Winship member Philip Santangelo, PhD, to drive the development of a cutting-edge programmable approach to prevent, treat and potentially cure diseases such as cancer, autoimmune disorders and infectious diseases.
President Joe Biden announced that a new federal agency within the U.S. Department of Health and Human Services has selected researchers at Winship Cancer Institute of Emory University among the inaugural recipients of funding to support transformative breakthroughs in health research including cancer and immunology.
The three-year, $24.8 million cooperative agreement from the Advanced Research Projects Agency for Health (ARPA-H) will drive the development of a cutting-edge programmable approach to prevent, treat and potentially cure diseases such as cancer, autoimmune disorders and infectious diseases. The ARPA-H funding supports work led by Winship member Philip Santangelo, PhD, a professor in the Wallace H. Coulter Department of Biomedical Engineering at Emory and Georgia Institute of Technology.
“It’s a tremendous honor for Emory to be the inaugural recipient of this very first ARPA-H Open BAA award, which will elevate and invigorate the visionary, life-changing health care research of our faculty,” said Emory President Gregory L. Fenves.
“We are grateful to have been selected to be a part of this historic health initiative. We look forward to collaborating with researchers across multiple departments, specialties, and organizations on these pivotal studies, facilitating medical advancements that could potentially enhance lives of countless people nationally and even worldwide,” said Suresh S. Ramalingam, MD, Winship’s executive director and Robero C. Goizueta Chair for Cancer Research in Emory University’s School of Medicine.
Many incurable, debilitating diseases, including certain types of cancer, lupus and some viral and bacterial infections, are caused or exacerbated by dysregulation of the immune system, which impairs the body’s ability to control the immune response and leaves a patient vulnerable to the disease. Immune modulation is a way to enhance the body’s immune response. The conventional methods of immune modulation — vaccines, antibodies, small molecules and cell-based therapies — face manufacturing complexities and limitations in their ability to engage immunity.
The Santangelo Lab will approach this challenge head-on by developing a novel class of mRNA-based drugs to precisely “turn on or turn off” genes in individual immune cells.
“By combining mRNA-encoded antigens with gene modulation technology, we will be able to radically enhance specific immune responses,” Santangelo said. “This technology, which operates transiently without modifying DNA, can offer a potential breakthrough in treating cancers, autoimmune disorders and infectious diseases.”
In addition to Winship’s cancer-focused research, Emory’s globally ranked immunology research programs are focused on autoimmunity, infectious diseases, transplantation, allergy, asthma, neuroimmunology and cardiovascular diseases, and include renowned leaders in immunology.
Rafi Ahmed, PhD, co-leader of Winship’s Cancer Immunology Research Program, will lead the studies focusing on strategies for overcoming T-cell exhaustion, which may have significant implications for treating cancer in the future. "With many cancers and chronic infections, the T-cells become dysfunctional, which we refer to as T-cell exhaustion," said Ahmed. T-cells are responsible for maintaining immune responses, and recognizing diverse antigens from threats such as pathogens, tumors, or the environment. Santangelo's system involves utilizing the mRNA platform to turn on and turn off RNA inhibitors to help modulate the cells of the immune system. One goal for the research team is to "figure out the best pathway to enhance T-cell function, to make T-cells more active and functional to kill the tumor" with Santangelo's novel approach.
Additionally, Iñaki Sanz, MD, also a member of Winship’s Cancer Immunology Research program, will lead the research studies focused on autoimmunity. “Both cancer and autoimmunity are regulated by abnormal immune responses,” Sanz said. “In cancer, a deficient immune response allows or even promotes tumor progression. Whereas, in autoimmunity, an exaggerated, dysregulated immune response is responsible for the disease. Interestingly, cancer immunotherapy is mediated by an autoimmune-like response against the tumor antigens and may in many cases trigger undesired autoimmune reactions. The ability to induce targeted fine regulation of different aspects of the immune response would enhance efficacy and reduce toxicity of cancer immunotherapy.”
The goal for this research is maximum impact. “The benefits will be far reaching, as the research proposed can be applied to any autoimmune disease and tailored to the specific case for each patient,” Sanz explained. Ahmed agrees. "If we can be successful at reversing T-cell exhaustion, this could have very broad applications to all cancers," he said.
The research plan unfolds through two parallel pathways. In the first, mRNA-based drugs will directly target immune cells within the body, triggering the expression of critical target proteins and meticulously modulating gene activity for improved immune function. The second approach employs a streamlined, fully functional cell-based therapy, combining messenger RNA-expressed antigens and gene modulators outside the body to prevent and treat diseases. These pathways, adaptable to diverse disease types, will be employed independently or in tandem to elevate vaccines and standard treatments.
The Santangelo Lab, which brings an outstanding track record of mRNA discovery and gene modulation research, will collaborate with other researchers from Winship, including Iñaki Sanz, MD, Christian Larsen, MD, DPhil, Rafi Ahmed, PhD, and Haydn Kissick, PhD, and John Lyons, MD, from Emory University, as well as researchers from Yale University (Richard Edelson, MD), the University of Georgia (R. Jeff Hogan, PhD and Eric Lafontaine, PhD) and Transimmune AG (Justin Duckworth) to carry out ARPA-H’s funding initiative.
"This substantial award reinforces and reflects the breadth, depth and advanced capabilities of Emory’s outstanding immunology community,” says Ravi Thadhani, MD, executive vice president for health affairs at Emory University.
Established in 2022, ARPA-H is a new federal agency that supports the development of high-impact research to drive biomedical and health breakthroughs. Emory has been selected to receive its first funding award to advance high-potential biomedical and health research that cannot be readily accomplished through traditional research or commercial activity.