Treating life-threatening bloodstream infections in combat situations is challenging, especially when the pathogen responsible is unknown. So, DARPA has called on Harvard’s Wyss Institute to use its groundbreaking biotech to fight this deadly threat.
We've previously reported on the use of ‘cellular backpacks’ placed on immune cells to help them fight cancer and heal traumatic brain injuries. Now, the researchers at Harvard University’s Wyss Institute for Biologically Inspired Engineering responsible for the tech have been contracted by DARPA, the Defense Advanced Research Projects Agency, to address a pressing threat to civilian and military populations.
The contract, worth up to US$12 million, is for DARPA’s new Synthetic Hemo-technologIEs to Locate and Disinfect (SHIELD) program, which aims to transform how the military manages and treats bloodstream infections, particularly in combat scenarios.
“We are thankful to DARPA for launching this program and selecting us to develop a novel class of therapeutics to defend against a broad range of pathogens,” said Wyss Institute core faculty member Samir Mitragorti, the DARPA-SHIELD project’s Principal Investigator. “Our goal is to develop a pathogen-agnostic treatment for defending human health in situations when the pathogen identity is unknown, or there is insufficient time to identify the pathogen.
Mitragorti developed the micrometer-sized ‘backpacks’ engineered to bind to the surface of specific immune cells, including pathogen-eating macrophages, inside and outside the body. Mitragorti and his team have already demonstrated in mice that when the backpacks are bound to macrophages and loaded with slow-release anti-inflammatory molecules, they kill tumor cells and slow the spread of cancer. But they can be used as more than a cancer treatment.
Wyss proposes addressing the SHEILD project’s aims by combining its cellular backpacks with another of its key technologies, FcMBL-mediated pathogen-binding. This tech involves genetically engineering mannose binding lectin (MBL), a substance that binds to foreign microorganisms and makes them more susceptible to destruction, which is linked to the Fc portion of an antibody. It was developed with prior DARPA support by the Wyss team led by founding director Donald Ingber and Michael Super, Director of ImmunoMaterials at the Wyss Institute. The team has demonstrated that FcMBL can bind to over 130 different pathogen types, including all major bacterial and fungal species that cause bloodstream infections and sepsis, the body’s extreme reaction to infection that can cause organ failure, tissue damage and death.
“It was a logical step to combine the FcMBL pathogen-binding technology with the cellular backpacks advanced in Professor Samir Mitragotri’s group, as this would harness the powers of FcMBL inside the bodies of infected individuals by activating critical cells of the innate immune system that are the body’s first line of defense,” said Super, who will act as a co-investigator with Mitragorti on the DARPA-SHIELD-funded project.
The resulting ‘FcMBL backpacks,’ injected directly into the bloodstream, will bind to macrophages and provide a constant stream of backpack-released anti-inflammatory molecules, keeping the immune cells activated for up to seven days. The backpack-toting macrophages can also patrol the body, particularly the liver and spleen, the major sites for clearing pathogens, eliminating them before they become a threat.
“The beauty of this groundbreaking project is that it combines two extremely powerful technologies that enable pathogen capture and immune cell activation, which synergize with each other when they are assembled into a living pathogen-killing machinery that can patrol inside the bodies of infected individuals,” said Ingber. “Easy to manufacture, store, and deploy, FcMBL backpacks could save the lives of many by enabling superior pathogen clearance in trauma patients at the site of injury.”
Source: Wyss Institute
