USC scientists have discovered a way to turn the body’s B cells into tiny surveillance machines and antibody factories that can produce antibodies specifically designed to destroy cancer cells or HIV, two of medicine’s most formidable enemies.
The research, published today in Biomedical Engineering of Naturedescribes a technique for editing the genes of immune cells called B cells, empowering them to fight off even the sneakiest invaders. The work is a major advance in harnessing the power of antibodies to treat diseases ranging from Alzheimer’s to arthritis.
“In some diseases or conditions, the natural antibodies produced by B cells just aren’t good enough,” said senior author Paula Cannon, a distinguished professor of molecular microbiology and immunology at the Keck School of Medicine of USC. “HIV is a very good example of that. It constantly mutates, staying one step ahead of any antibody thrown at it. We thought a checkmating move might be to coax B cells into producing an antibody that was so broad in its ability to ‘see’ HIV that HIV couldn’t easily mutate around it.”
The beauty of the technique, the researchers said, is that it can be adapted to produce a wide range of different antibodies.
“It’s a technology for reprogramming B cells that could be applied to almost anything you can imagine involving an antibody,” said first author Geoffrey Rogers, a research associate and senior postdoctoral fellow in Cannon’s lab. “We think we’ll be able to completely customize everything involving the antibody.”
For this project, the researchers were inspired by chimeric antigen receptor (CAR) T cells, “living medicines” designed to act on specific things. They have revolutionized the treatment of blood cancers such as leukemia and lymphoma. With CAR T treatment, T cells (sister cells of B cells) are taken from a patient’s blood and genetically modified to identify cancer cells by recognizing a marker on their surface. Millions of the cells are then infused into the patient’s body, where they fight the disease and then disappear.
B cells behave differently, making them better suited to combat chronic diseases. They function as a security system and antibody factory, and reside long-term in the bone marrow, lymph nodes and spleen, and are activated when needed.
To create these tiny fighters, Cannon and Rogers used CRISPR gene-editing methods to place the instructions for the custom antibodies at the exact site in the B cell’s DNA where antibodies are naturally produced. This trick means that B cells can be reprogrammed as biofactories that produce the personalized antibodies. And, just as normal antibodies respond to vaccination, the reprogrammed B cells could also be stimulated to increase their production.
The researchers were able to observe the antibodies in action by using tonsil tissue to replicate an immune system in a dish.
The researchers are working with the USC Stevens Center for Innovation to license the technology for commercial use. The USC Stevens Center helps scientists take their discoveries from the lab to the marketplace.
“We’re really excited to try to bring this to biotech companies,” said Erin Overstreet, executive director of the USC Stevens Center. “This could be a fundamental shift in how we approach certain diseases.”
In addition to Cannon and Rogers, other authors on the paper include Chun Huang, Atishay Mathur, Xiaoli Huang, Hsu-Yu Chen, Kalya Stanten, Heidy Morales, Chan-Hua Chang and Eric Kezirian, all of USC.
The work was supported by grants from the National Institutes of Health (HL156274, AI164561, AI164556, and MH130178).