USC scientists have discovered a way to turn the body’s B cells into tiny surveillance machines and antibody factories that can pump out antibodies specifically designed to destroy cancer cells or HIV, two of medicine’s most formidable foes. .

The research, published today in Nature Biomedical Engineering, describes a technique for editing the genes of immune cells called B cells, turbocharging them to fight off even the meanest invaders. The work is an important advance in harnessing the power of antibodies to treat conditions ranging from Alzheimer’s disease to arthritis.

“In some diseases or conditions, the natural antibodies produced by B cells are not good enough,” said senior author Paula Cannon, a distinguished professor of molecular microbiology and immunology at USC’s Keck School of Medicine. “HIV is a very good example of this. It’s constantly changing, keeping one step ahead of whatever antibody is thrown at it. We thought that a mat move could convince B cells to produce an antibody that was so broad in its ability to him to ‘see’ HIV that HIV could not easily change around him.”

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 can be applied to almost anything you can imagine having to do with 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 about antibodies.”

For this project, the researchers took inspiration from chimeric antigen receptor (CAR) T cells, “living drugs” designed to target specific things. They have revolutionized treatment for blood cancers such as leukemia and lymphoma. With CAR T treatment, T cells – the sister cells to B cells – are removed from the patient’s blood and genetically modified to identify cancer cells by recognizing a marker on their surface. Millions of cells are then introduced into the patient’s body, where they fight disease and then disappear.

B cells behave differently, making them better suited to fight chronic disease. They function as a security system and as an antibody factory, staying for a long time in the bone marrow, lymph nodes and spleen – and turning on when needed.

To make these little warriors, Cannon and Rogers used CRISPR gene-editing methods to place the instructions for personalized antibodies in the exact spot in the DNA of B cells, where antibodies are naturally produced. This trick means that B cells can be reprogrammed as biofactories that make custom antibodies. And just as regular antibodies respond to vaccination, reprogrammed B cells can also be stimulated to increase their production.

The researchers were able to observe the antibodies at work 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 help try and bring this to biotech companies,” said Erin Overstreet, executive director of the USC Stevens Center. “This could be a fundamental change in the way we approach certain diseases.”

In addition to Cannon and Rogers, other authors of the paper are 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).