The left image shows the immune organ-on-chip, where the organoids (right) are grown to study the response of human donors. The right image shows development of types of immune cells relevant to the antibody response. (Credit: Ankur Singh)
To better understand why some cancer patients struggle to fight off infections, Georgia Tech researchers have created tiny lab-grown models of human immune systems.
These miniature models — known as human immune organoids — mimic the real-life environment where immune cells learn to recognize and attack harmful invaders and respond to vaccines. Not only are these organoids powerful new tools for studying and observing immune function in cancer, their use is likely to accelerate vaccine development, better predict disease treatment response for patients, and even speed up clinical trials.
“Our synthetic hydrogels create a breakthrough environment for human immune organoids, allowing us to model antibody production from scratch, more precisely, and for a longer duration,” said Ankur Singh, Carl Ring Family Professor in the George W. Woodruff School of Mechanical Engineering and professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory.
“For the first time, we can recreate and sustain complex immunological processes in a synthetic gel, using blood, and effectively track B cell responses,” he added. “This is a gamechanger for understanding and treating immune vulnerabilities in patients with lymphoma who have undergone cancer treatment — and hopefully other disorders too.”
Led by Singh, the team created lab-grown immune systems that mimic human tonsils and lymph node tissue to study immune responses more accurately. Their research findings, published in the journal Nature Materials, mark a shift toward in vitro models that more closely represent human immunology. The team also included investigators from Emory University, Children’s Hospital of Atlanta, and Vanderbilt University.
Designing a Tiny Immune System Model
The researchers were inspired to address a critical issue in biomedical science: the poor success rate of translating preclinical findings from animal models into effective clinical outcomes, especially in the context of immunity, infection, and vaccine responses.
“While animal models are valuable for many types of research, they often fail to accurately mirror realistic human immune biology, disease mechanisms, and treatment responses,” said Monica (Zhe) Zhong, a Bioengineering Ph.D. student and the paper’s first author. “To address this, we designed a new model that faithfully replicates the unique complexity of human immune biology across molecular, cellular, tissue, and system levels.”
The team used synthetic hydrogels to recreate a microenvironment where B cells from human blood and tonsils can mature and produce antibodies. When immune cells from healthy donors or lymphoma patients are cultured in these gel-like environments, the organoids support longer cell function, allowing processes like antibody formation and adaptation to occur — similar to the human body. Utilizing the organoids for individual patients helps predict how that individual will respond to infection.
The models also enable researchers to control and test immune responses under various conditions. The team discovered that not all tissue sources are the same, and tonsil cells struggled with longevity issues. They used a specialized setup to study how healthy immune cells react to signals that help them fight infections, which failed to trigger the same response in cells from lymphoma survivors who seemingly have recovered from immunotherapy treatment.
Using organoids embedded in a novel immune organ-on-chip technology, the team observed that immune cells from lymphoma survivors treated with certain immunotherapies do not organize themselves into specific “zones,” the way they normally would in a strong immune response. This lack of organization may help explain some immune challenges cancer survivors face, as evidenced by recent clinical findings.