Long CAR Journey

We last reported on Chimeric Antigen Receptor (CAR) T-cell immunotherapy treatments in a blog from 2018, where it was noted that progress within solid tumour cancers was still at early stages. An interesting briefing published recently in Nature Medicine shows the potential benefit of such approaches by highlighting a previously unheralded early success: a person surviving eighteen years after first generation CAR-T treatment for active neuroblastoma, after the failure of previous standard treatments.

The trial was made up of eleven people with, and eight without, active disease at the time of infusion. Of the eight people with no active disease, five remained disease free at the time of their last follow-up. Of the eleven with active disease, three had a complete response, and while one of those ultimately relapsed, two survived: one for eight years until lost to follow-up, and another for over eighteen years. The paper states:

Patient 1,144, who is alive at more than 18 years after infusion, had bone lesions before receiving CAR-T and attained a complete remission. She has never required any other therapy and is likely the longest-surviving patient with cancer who received CAR-T therapy.

Li, CH., Sharma, S., Heczey, A.A. et al (2025)

This also means, however, that twelve of the nineteen trial patients did relapse following the trial, and all twelve died between two months and seven years after treatment. This is because cancer, as we've noted previously, is infamously difficult to treat. Across its many subtypes, we encounter cells that were once part of us, but having forgotten how to play that role, they live on, retaining only a blind biological imperative to divide and survive. Biology is a tough opponent, and so CAR-T immunotherapies are a key use of synthetic biology in medical context to allow humanity to fight fire with fire.

At heart, this is a battle of biological vigilance. CAR-T therapies create immune cells specialised for a specific cancerous target, and ideally these immune cells will persist in the body for an extended period, remaining on patrol to pick up any cells that escaped the initial treatment. Against this enhanced immunosurveillance, cancer answers with immunosuppression, using biological mechanisms to deter and evade the immune response. Right now, in solid tumours, suppression seems to have the edge over surveillance in the longer term. But Patient 1144 stands as an example of what perfecting these techniques might deliver, offering hope that The Emperor of All Maladies might one day be dethroned.