A joint research effort between the University of Virginia School of Medicine and the University of Michigan has resulted in the development of a novel monoclonal antibody aimed at combating sepsis, a lethal systemic infection. This breakthrough could also lead to treatments for various other inflammatory conditions, including autoimmune disorders.
Initial trials on mice have demonstrated the versatility of this antibody, showing "revolutionary potential" for treating life-threatening inflammatory diseases, as described in the researchers' new paper. Potential uses may extend to acute respiratory distress syndrome (ARDS), which gained prominence during the COVID-19 pandemic, and ischemia-reperfusion injury, a significant issue in organ transplantation.
The research has provided valuable insights into the molecular causes of sepsis and could lead to an important diagnostic tool for monitoring patients.
"This is a game-changing discovery that can redefine treatment standards," stated Jianjie Ma, Ph.D., from UVA's Department of Surgery and UVA Cancer Center. "By merging expertise in basic science, innovation, and translational medicine, we've engineered an unprecedented antibody with the power to save countless lives from sepsis and other severe inflammatory diseases."
The study appears in Nature Communications.
Nature CommunicationsSepsis affects up to 50 million people annually worldwide, claiming around 11 million lives. It is a leading cause of mortality in U.S. hospitals, with fatality risks escalating with each hour left untreated. Sepsis occurs when the immune response spirals out of control due to an infection, potentially causing organ failure and death. Even with aggressive treatment, up to 40% of patients with severe sepsis succumb.
Ma and his team hope their new antibody will be the first treatment targeting the immune system dysregulation that underlies sepsis, aiming to prevent cytokine storms that garnered attention during the pandemic by halting the body's overactive immune response before organ damage sets in.
Preliminary tests suggest the antibody can achieve this without the adverse side effects of current sepsis treatments. In initial studies, it was effective at stopping inflammatory cytokines and restoring macrophage function while protecting against sepsis-induced lung injury.
$The researchers note that the tools used to produce the antibody may also aid in detecting and monitoring sepsis through a platform called PEdELISA, capable of quantifying six cytokines from a single drop of plasma within two hours.
"Our humanized antibody demonstrates both safety and efficacy in blocking cytokine storms and restoring healthy immune functions," said Yongqing Li, MD, Ph.D., from the University of Michigan Medical School. "Beyond treating acute infections, it holds promise for addressing diseases resulting from faulty immune regulation, such as autoimmune disorders, cancer, and diabetes."
The researchers plan to launch a clinical trial of the antibody at UVA Health and Virginia Commonwealth University. The antibody has substantial translational potential when used with PEdELISA.
"Integrating PEdELISA with this antibody therapy allows for a comprehensive approach to sepsis management," said industry partner Guidong Zhu. "It enables earlier diagnosis, continuous monitoring, timely therapeutic adjustments, and a better chance for complete recovery."
During the development of their antibody, researchers uncovered critical molecular insights into sepsis mechanisms, identifying feedback loops in macrophages that drive uncontrolled inflammation. The new antibody interrupts these processes.
The goal is to leverage breakthroughs like this to overcome major medical challenges, aligning with UVA's Paul and Diane Manning Institute of Biotechnology mission.
"UVA is proud of this groundbreaking discovery," said Melina R. Kibbe, MD, dean of UVA School of Medicine. "We're eager to collaborate with clinicians and industry partners to transition this bench discovery into the clinic where it could be lifesaving."