Scientists have developed an organ-on-a-chip platform that replicates age-related immune decline, offering a long-missing tool for testing cancer vaccines in older adults.
Researchers at the Terasaki Institute have announced a pioneering organ-on-a-chip platform capable of replicating age-dependent immune responses, offering an important tool for assessing how cancer vaccines perform in older adults. The innovation, developed in the laboratory of Dr Vadim Jucaud, aims to fill a longstanding gap in preclinical testing, where the effects of ageing on the immune system are frequently overlooked despite their importance.
Addressing the challenge of immunosenescence
Cancer disproportionately affects older adults, yet most laboratory models fail to reflect how the immune system naturally weakens with age. This process – known as immunosenescence – significantly reduces the effectiveness of cancer vaccines and other immunotherapies. Conventional two-dimensional cell culture systems cannot replicate the complex, age-specific interactions required to predict how these therapies will behave in real patients.
Recognising this limitation, Dr Jucaud’s team set out to design a more physiologically relevant system. Their solution is a lymph node paracortex-inspired organ-on-a-chip platform that simulates the key parts of the immune responses triggered by cancer vaccinations. These include antigen presentation, activation of antigen-specific T cells and subsequent tumour-directed cytotoxicity.
Dr Vadim Jucaud holds the lymph node–on-a-chip device developed by him and his lab to model age-dependent immune responses to cancer vaccination. Credit: Terasaki Institute for Biomedical Innovation.
A platform that reveals age-related differences
The research team tested the platform using lymphocytes from both young and older donors. The system successfully reproduced the functional disparities that emerge within the immune system as it ages – differences that traditional 2D models fail to detect.
In their findings, young antigen-presenting cells showed stronger peptide presentation than those from older individuals.
In their findings, young antigen-presenting cells showed stronger peptide presentation than those from older individuals. This heightened activity produced more robust activation of antigen-specific T cells, ultimately resulting in greater cytotoxicity against cancer cells. Crucially, these variations appeared only when using the organ-on-a-chip system, highlighting its ability to discover meaningful biological distinctions.
“This work introduces our lymph node on-a-chip platform for cancer vaccine testing,” said Dr Vadim Jucaud, principal investigator and assistant professor at the Terasaki Institute. “Unlike traditional 2D models, this advanced system replicates age-related immune responses, which is critical because older adults face the highest cancer risk and often have diminished immunity. By accurately modelling these conditions in vitro, our platform enables more reliable insights into cancer vaccine performance, therefore accelerating development and improving outcomes.”
Implications for immunotherapy development
By capturing the true biological impact of ageing, the new platform provides researchers with a more accurate way to evaluate emerging cancer vaccines and immunotherapies. This could prove particularly valuable for the development of next-generation treatments specifically tailored to older patients, who represent most cancer cases yet are often under-represented in early-stage research.
By capturing the true biological impact of ageing, the new platform provides researchers with a more accurate way to evaluate emerging cancer vaccines and immunotherapies.
The researchers believe the technology could ultimately help to reshape vaccine development pipelines by ensuring age-related immune decline is properly considered from the outset. In doing so, it aims to support the creation of therapies that are not only effective in theory but beneficial for the patients who need them most.
As cancer vaccine research continues to progress, tools such as this organ-on-a-chip model may play a vital role in bridging the gap between laboratory success and clinical effectiveness – providing a clearer, more reliable understanding of how the ageing immune system responds to innovative cancer treatments.
Related topics
Cancer research, Immuno-oncology, Immuno-oncology therapeutics, Immunology, In Vitro, Lab-on-a-Chip, Microfluidic Technology, Oncology, Organ-on-a-Chip, Translational Science, Vaccine, Vaccine development
