A first-in-human clinical trial of an immune rejuvenation therapy designed to restore the function of worn-out T cells is expected to begin later this year, building on research led by UCL scientists into the mechanisms of immune aging.
The Phase 1 trial will focus on exhausted or senescent T cells, which accumulate with age and in chronic disease and become less effective at coordinating immune protection.
Researchers hope that metabolically resetting these cells may help the immune system regain characteristics associated with younger, healthier immune responses. The work may have clinical utility for diseases such as cancer, HIV and dementia.
Our immune system protects us from infection, cancer and disease. However, as we age, some immune cells become exhausted and lose their ability to function effectively. This process, known as immune aging, can leave people more vulnerable to illness and less able to respond to health challenges.
The new therapy, developed by biotech company SenTcell founded by Dr Alessio Lanna (UCL Medicine), is designed to rejuvenate these worn-out immune cells. Rather than attacking diseased cells directly, it works by restoring the immune system's natural ability to recognize and respond to threats.
The treatment is a liquid formulation administered by intramuscular injection, similar to many commonly used vaccines. Once delivered, it is designed to reprogramme key pathways that drive immune dysfunction, helping immune cells regain characteristics of younger, healthier cells.
The goal is to improve immune resilience, enhance protection against disease and ultimately support healthier aging.
Dr Lanna said: "People living with HIV are now able to live long and healthy lives thanks to major advances in treatment, but many still experience features of accelerated immune aging. Similar patterns of immune dysfunction are also seen in cancer and other chronic diseases.
"This trial is an important step towards testing whether we can safely rejuvenate exhausted immune cells and restore aspects of healthy immune function. Our goal is to help establish immune rejuvenation as a new way of treating diseases linked to immune aging and dysfunction."
The trial builds on research suggesting that some dysfunctional T cells – a type of white blood cell that helps coordinate the body's immune response – can be restored to a more youthful, functional state. Researchers are focusing on CD4+ T cells, often described as the "conductors" of the immune system because they help direct other immune cells to respond to infection, cancer and disease.
Inside every cell, chromosomes are protected by structures called telomeres, which sit at their ends like protective caps. Telomeres help shield genetic material from damage and gradually shorten as cells divide over time, making them a well-established marker of biological aging.
Previous laboratory studies suggest that rejuvenated CD4+ T cells may be able to release telomere-containing structures into the bloodstream. Researchers have termed these structures "telomere Rivers" and are investigating whether they could help explain how rejuvenated immune cells influence the health and function of other tissues throughout the body. This idea remains under active investigation and has not yet been demonstrated in humans.
The research programme has received support through the Medicines and Healthcare products Regulatory Agency's (MHRA) Innovative Licensing and Access Pathway (ILAP), recognising its potential to address significant unmet needs associated with age-related immune decline and immune dysfunction.
UCL researchers are preparing for Phase 1 of the trial, which will carefully select adult participants and is expected to focus initially on people with evidence of immune dysfunction, including immune aging and chronic viral infection. Participants will undergo detailed immune profiling before and after treatment.
Investigators will look at whether the therapy can restore features of healthy immune function. As an early-stage trial, the primary goals are safety and biological activity rather than demonstrating clinical benefit.
If successful, the programme could establish immune rejuvenation as a new therapeutic approach: restoring the immune system's protective capacity instead of targeting each pathogen or disease process separately.
Researchers believe the strategy could eventually have relevance for conditions characterised by immune exhaustion, including chronic infections, autoimmune disease and cancer, while also informing broader efforts to improve healthy aging.
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