Carl R. Woese Institute for Genomic Biology

The adaptive immune system is a biological marvel, able to respond flexibly to a never-ending parade of pathogens. To produce effective germ-fighting antibodies, though, immune cells still need time and luck. With the support of a new award from the Ono Pharma Foundation, research to develop an innovative laboratory process will help shortcut these constraints on the immune system, enabling more rapid discovery of therapeutics targeting both infectious diseases and cancer.

Assistant Professor of Chemistry Angad Mehta (MMG) will lead the research funded by the $1.035 M grant. The proposed research is aligned with the mission of the Ono Pharma Foundation to enable innovation in the treatment of disease. The Foundation has a particular interest in providing resources for emerging scientists.

“This Ono funding project will help my lab to continue to push forward this research in truly transformative directions,” Mehta said. “I am most excited about our efforts in synthetic immunology that will result in the development of in vitro immune-like systems that can be used for rapidly developing and evolving therapeutically relevant proteins like antibodies directly in human cells.”

Mehta’s research focuses on a particular kind of cell in the immune system called a B cell. Each person produces a wide array of B cells, each of which can detect a certain type of foreign substance, called an antigen, that may help it identify a certain type of pathogen. When a B cell finds its antigen, it can be activated to start producing a large quantity of antibodies that will stick to the antigen (usually an invading virus or bacterium) and tag it for destruction. B cells therefore function as efficient antibody factories.

Working as part of collaborative HHMI EPI group led by Prof. Wilfred van der Donk, Mehta’s lab has previously engineered B cells to evolve potent antibodies against H5N1, the virus that causes avian influenza, then used a laboratory process called directed evolution to improve the ability of those antibodies to attack the virus. This approach, which will be central to the new research project, leverages the ability of cells from human immune system to produce a wide variety of possible antibodies and amplify and select the best ones, while bypassing the need for waves of infection and giving the process a push in the right direction. Mehta’s team will work to streamline the discovery and refinement of new useful antibodies.

“These studies serve as a foundation for the Ono project where we will engineer and fine tune human immune cells as a chassis for continuous laboratory evolution and biologics development,” Mehta said. “We will be combining this technology with single-cell/single-molecule approaches and machine learning to accelerate the development of biologics for human health.”

Past antibody discovery has led to safer and more effective treatments for many types of health conditions, including immune disorders, migraines, and many types of cancer, as well as faster and more accurate diagnostic testing, reinforcing the promise of this area of medical research.

See also Prof. Angad Mehta receives $1 million “Ono Initiative” award for antibody, biologics research