17 June 2024

A simple intervention may help improve the effectiveness of CAR-T treatment, biomedical engineers have reported.

The US-based engineers developed a biodegradable scaffold material to be locally injected under the skin, described as a “pseudo lymph node”. By carrying molecules to stimulate T cells, it can be used to boost the effectiveness of CAR-T cells after administration, they say.

To highlight the need for improving CAR-T cell therapy effectiveness, they point to a study in their local hospital of 100 blood cancer patients who underwent the therapy. 20% did not respond to treatment and 24% only had partial responses. The researchers say treatment failure might be caused by poor quality cell products or the cells not persisting long enough in patients – or the cells becoming exhausted.

So far, the team’s intervention has been tested on laboratory mice. The intervention involves injecting a biodegradable material into the mice, which carries IL-2 to stimulate the proliferation of T cells, and anti-CD3 and anti-CD28 antibodies to activate T cells.

The researchers say it increased the number of CAR-T cells in the mice, including CAR-T cells primed to kill cancer cells. As a result, the ‘pseudo-lymph node’ curbed tumour growth, and prolonged survival in the mice.

Professor Donald Ingber, of Harvard Medical School and Boston Children’s Hospital, said: “This study demonstrates the power of using engineering to mimic multicellular interactions that are central to our immune system's ability to fight off cancers.  This technology could go a long way in changing the lives of many cancer patients receiving CAR-T therapies who are not yet benefitting from them.”

Developer Professor David Mooney, of the Wyss Institute for Biologically Inspired Engineering, Harvard, said: “Although our strategy needs to be translated to human needs and settings, it potentially offers a safe, and simple avenue on which to further improve CAR-T cell therapies in patients with poor responses. It also could have future potential to simplify the extremely arduous and expensive manufacturing of CAR-T cell by transferring part of the process into patients’ bodies.”


Zhang DKY, Brockman JM, Adu-Berchie K, Liu Y, Binenbaum Y, de Lázaro I, Sobral MC, Tresa R, Mooney DJ. (2024) “Subcutaneous biodegradable scaffolds for restimulating the antitumour activity of preadministered CAR-T cells.” Nature Biomedical Engineering, 3 June 2024, doi: 10.1038/s41551-024-01216-4.

Link: https://www.nature.com/articles/s41551-024-01216-4

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