Reprogramming B cells to produce custom antibodies

Researchers at the University of Southern California (USC) have discovered a technique to reprogramme the immunoglobulin locus of B cells, enabling them to produce specially designed antibodies, that are not induced by immunisation, to destroy cancer cells or HIV.

Paula Cannon, Distinguished Professor of Molecular Microbiology & Immunology at the Keck School of Medicine of USC and senior author of the study, explained: “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 team stated that the new technique can be adapted to produce a wide range of different antibodies. B cells’ behaviour makes them ideal for combatting chronic conditions, as they function as a security system and antibody factory, living long-term in the bone marrow, lymph nodes and spleen.

With Cannon, first author Geoffrey Rogers, research associate and senior postdoctoral fellow in Cannon’s lab, utilised CRISPR gene editing methods to place the instructions for custom or non-natural antibodies at the exact site in the B cell’s DNA where antibodies are naturally produced. The antibodies were observed in a tonsil organoid model of immunisation. Like how regular antibodies respond to vaccination, the reprogrammed B cells could be stimulated to increase their output.

Now, the scientists are working with the USC Stevens Center for Innovation to license the technology for commercial use. Erin Overstreet, executive director of the USC Stevens Center concluded: “We’re really excited to help try and bring this to biotech companies…This could be a fundamental shift in how we approach certain diseases.”

This study was published Nature Biomedical Engineering.