These small immune system replicas, called human immune organoids, replicate the actual setting where immune cells learn to spot and combat harmful invaders and react to vaccines. They are not only effective tools for examining and analyzing immune behavior in cancer, but their application is expected to speed up vaccine creation, enhance predictions of how patients will respond to treatments, and even hasten clinical trials.
To gain insight into why certain cancer patients face challenges in fighting infections, researchers at Georgia Tech have developed tiny, lab-grown representations of human immune systems.
These small-scale models, known as human immune organoids, reproduce the authentic environment wherein immune cells are trained to identify and eliminate harmful threats and respond to vaccination efforts. Their innovative design not only aids in studying immune function in cancer but is anticipated to quicken vaccine development, improve the forecasting of patient treatment responses, and enhance the speed of clinical trials.
“Our synthetic hydrogels create a groundbreaking setting for human immune organoids, enabling us to more accurately and sustainably model antibody production from the base up,” noted Ankur Singh, Carl Ring Family Professor at the George W. Woodruff School of Mechanical Engineering and a professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory.
“We can now recreate and maintain intricate immunological activities within a synthetic gel, utilizing blood, while effectively monitoring B cell reactions,” he added. “This represents a significant shift for understanding and addressing immune weaknesses in lymphoma patients post-cancer treatment—and potentially in other diseases as well.”
Under Singh’s leadership, the team developed lab-created immune systems that imitate human tonsils and lymph nodes, enabling a more precise study of immune reactions. Their research, published in Nature Materials, marks a movement towards in vitro models that closely correspond to human immunology. The project included collaborators from Emory University, Children’s Hospital of Atlanta, and Vanderbilt University.
Creating a Compact Immune System Model
The researchers aimed to tackle a pressing concern in biomedical science: the lack of success in translating animal model findings into effective clinical applications, especially related to immunity, infection, and vaccine reactions.
“While animal models are valuable in various research fields, they frequently do not accurately reflect human immune biology, as well as disease mechanisms and treatment reactions,” stated Monica (Zhe) Zhong, a Bioengineering Ph.D. student and the lead author of the study. “To solve this problem, we devised a new model that genuinely mirrors the distinct complexity of human immune biology at molecular, cellular, tissue, and systemic levels.”
The researchers utilized synthetic hydrogels to recreate an environment where B cells extracted from human blood and tonsils can grow and generate antibodies. When immune cells from healthy individuals or lymphoma patients are placed in these gel-like settings, the organoids promote longer-lasting cell activity, enabling processes like antibody production and adaptation to take place—much like within the human body. This helps in predicting individual responses to infections.
The models also allow researchers to manipulate and evaluate immune reactions under various circumstances. The team found that not all tissue sources behave identically, noting that tonsil cells faced challenges with longevity. They set up a specialized system to observe healthy immune cell reactions to stimuli that assist in infection combat, which did not elicit the same response from cells of lymphoma survivors who appeared to have recovered from immunotherapy.
By employing organoids integrated within a new immune organ-on-chip technology, the team determined that immune cells from lymphoma survivors treated with specific immunotherapies did not form typical “zones,” as they normally would during a robust immune response. This lack of structured organization may clarify some immune-related difficulties faced by cancer survivors, as highlighted by recent clinical data.
A Revolutionary Technology
This investigation serves primarily those involved in infectious diseases, cancer research, immunology, and healthcare professionals committed to enhancing patient outcomes. Through the examination of these miniature immune systems, they can uncover reasons why current treatments may fall short and explore inventive strategies to strengthen immune protection.
“Lymphoma patients who received CD20-targeted therapies frequently experience an increased vulnerability to infections that can persist for years following their treatment. Understanding these long-term effects on antibody reactions could be crucial for improving safety and quality of life for lymphoma survivors,” explained Dr. Jean Koff, an associate professor in Hematology and Oncology at Emory University’s Winship Cancer Institute and a co-author of the study.
“This technology offers deeper biological insights and a novel method for tracking the recovery of immune deficiencies over time. It could allow clinicians to better identify patients who stand to gain from specific interventions aimed at reducing infection risks,” Koff added.
A further significant and hopeful aspect of this research is its scalability: an individual researcher can produce hundreds of organoids in one session. The model’s capacity to address different groups—both healthy and immunosuppressed patients—greatly enhances its applicability for vaccine and treatment testing.
According to Singh, who leads the Center for Immunoengineering at Georgia Tech, the research team is already expanding their studies, including developing cellular therapies and a model for aged immune systems to tackle questions related to aging.
“Ultimately, this work primarily impacts cancer patients and survivors who often battle weakened immune responses and might not react effectively to conventional treatments like vaccines,” Singh elucidated. “This breakthrough could pave the way for innovative methods to enhance immune defenses, thereby aiding vulnerable patients in achieving better health and more complete recoveries.”
The research received initial support from the Wellcome Leap HOPE program, which subsequently led to enhanced funding, including a recent $7.5 million grant from the National Institute of Allergy and Infectious Diseases.
