Scientists have found a way to transform the body’s B cells into miniature surveillance units and antibody factories that can produce tailor-made antibodies to eliminate cancer cells or HIV, two of medicine’s toughest adversaries.
USC researchers have devised a method to convert the body’s B cells into miniature surveillance units and antibody factories that can produce custom antibodies to eradicate cancer cells or HIV, two of the most challenging foes in medicine.
The study, recently published in Nature Biomedical Engineering, outlines a process for modifying the genes of B cells, enhancing them to combat even the most elusive invaders. This development is a significant stride in utilizing antibodies to address conditions ranging from Alzheimer’s disease to arthritis.
“In certain diseases or situations, the naturally produced antibodies by B cells do not suffice,” mentioned senior author Paula Cannon, a Distinguished Professor of Molecular Microbiology & Immunology at the Keck School of Medicine of USC. “HIV serves as a prime example of this. It constantly mutates, staying ahead of the antibodies targeted against it. We speculated that a strategic move might involve motivating B cells to generate an antibody with such broad recognition of HIV that the virus could not easily evade it.”
The significance of this technique, as per the researchers, is its adaptability to produce a wide array of diverse antibodies.
“It’s a method for reprogramming B cells that could be employed for almost any situation in which an antibody is required,” explained first author Geoffrey Rogers, a research associate and senior postdoctoral fellow in Cannon’s lab. “We anticipate the ability to fully customize every aspect of the antibody.”
For this project, researchers drew inspiration from chimeric antigen receptor (CAR) T cells, which are “living drugs” engineered to target specific entities. They have transformed the treatment of blood cancers such as leukemia and lymphoma. Through CAR T therapy, T cells, closely related to B cells, are extracted from a patient’s blood and genetically manipulated to recognize cancer cells by sensing a surface marker. These cells are then introduced into the patient’s body in large quantities, where they combat the disease before disappearing.
B cells exhibit distinct behavior, making them more apt for battling chronic conditions. They serve as a security system and antibody factory, residing long-term in the bone marrow, lymph nodes, and spleen, and activating when necessary.
To produce these minute combatants, Cannon and Rogers utilized CRISPR gene editing techniques to embed the instructions for personalized antibodies directly into the B cell’s DNA where antibodies are naturally produced. This approach enables the reprogramming of B cells as biofactories to manufacture the custom antibodies. Similar to how conventional antibodies react to vaccines, the reprogrammed B cells can also be prompted to heighten their production.
Scientists were able to observe the antibodies in action by employing tonsil tissue to simulate an immune system in a laboratory setting.
The researchers are collaborating with the USC Stevens Center for Innovation to secure the technology for commercial purposes. The USC Stevens Center aids scientists in guiding their discoveries from the laboratory to the market.
“We are thrilled to aid in the potential availability of this technology to biotech companies,” stated Erin Overstreet, executive director of the USC Stevens Center. “This could herald a fundamental shift in how we tackle certain diseases.”
In addition to Cannon and Rogers, other contributors to the study include Chun Huang, Atishay Mathur, Xiaoli Huang, Hsu-Yu Chen, Kalya Stanten, Heidy Morales, Chan-Hua Chang, and Eric Kezirian, all affiliated with USC.
This research received funding from the National Institutes of Health (HL156274, AI164561, AI164556, and MH130178).
