New Technique Reprograms B Cells to Produce Custom Antibodies

USC scientists have pioneered a method to genetically modify B cells, turning them into surveillance machines and antibody factories that can pump out specially designed antibodies to destroy cancer cells or HIV.

This technique, published in Nature Biomedical Engineering, involves editing the genes of B cells to enhance their ability to fight persistent invaders. Paula Cannon, a senior author of the paper, highlighted the limitations of natural antibodies, particularly against rapidly mutating viruses like HIV. “In some diseases or conditions, the natural antibodies made by B cells are just not good enough. HIV is a very good example of that. It mutates constantly, keeping one step ahead of whichever antibodies are being thrown at it. We thought a checkmate move might be persuading B cells to make an antibody that was so broad in its ability to ‘see’ HIV that HIV couldn’t easily mutate around it."

The versatility of this method allows for the production of a wide range of customized antibodies. Geoffrey Rogers, the study's first author, emphasized the potential applications: "It’s a technology for reprogramming B cells that could be applied to almost anything you can imagine dealing with an antibody."

Inspired by the success of CAR T cell therapy in treating blood cancers, the researchers adapted similar principles for B cells. Unlike T cells, B cells reside long-term in the bone marrow, lymph nodes, and spleen, making them ideal for chronic conditions. Using CRISPR gene editing, the team inserted instructions for custom antibodies directly into the B cell’s DNA, enabling these cells to act as biofactories.

The reprogrammed B cells can be stimulated to increase antibody production, similar to how natural antibodies respond to vaccination. The researchers validated their approach using tonsil tissue to simulate an immune system.

USC is collaborating with the USC Stevens Center for Innovation to commercialize this technology. Erin Overstreet, the center's executive director, expressed optimism about the potential impact: “This could be a fundamental shift in how we approach certain diseases.”