Study shows ageing can reduce effectiveness of CAR-T cell cancer therapy

New Delhi, May 21 Age-related decline in the immune system can have a measurable impact on CAR-T cell therapy -- one of the most advanced forms of cancer immunotherapy, according to a study.

CAR-T therapy works by engineering a patient's T cells to recognise and destroy cancer cells.

The study led by Swiss researchers found that CAR-T cells from aged mice had poor mitochondrial function, lower "stemness," and reduced antitumour activity.

It was due to a drop in levels of nicotinamide adenine dinucleotide (NAD) -- a molecule essential for cellular energy and metabolism of mitochondria, said the team from the University of Lausanne (UNIL), the Lausanne University Hospital (CHUV), the Geneva University Hospitals (HUG) and the Ecole Polytechnique Fédérale de Lausanne (EPFL).

"CAR-T cells from older individuals are metabolically impaired and significantly less effective. What's exciting is that we were able to rejuvenate these aged cells by restoring their NAD levels -- reviving their antitumour function in preclinical models," said Dr. Helen Carrasco Hope.

"Our findings strengthen the growing recognition that ageing fundamentally reshapes immune cell function and metabolism.

"They highlight the urgent need to model age more accurately in preclinical studies so that therapies are developed with the real-world cancer population in mind -- where most patients are older adults," Hope said.

For the study, published in the journal Nature Cancer, the team used NAD-boosting compounds currently under clinical investigation for other conditions, demonstrating that this approach is translatable and potentially applicable in humans.

"This is a major step toward personalised and age-conscious immunotherapy," said senior author Dr. Nicola Vannini.

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The study adds to a growing body of work showing that age is not just a chronological number, but a biological factor that can shape therapy response.

The researchers called for age to be systematically considered in the development and evaluation of cell-based immunotherapies.

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