T cell cytokine ‘backpacks’ target solid tumours

By Ben Hargreaves

- Last updated on GMT

(Image: Pixabay/Allinonemovie)
(Image: Pixabay/Allinonemovie)
Researchers from MIT have devised a way for T cells to be engineered to carry nanoparticle ‘backpacks’ that can deliver the payload only when interacting with the target tumour cells.

The pharma industry has so far achieved notable success in targeting ‘liquid tumours’ by harnessing T cells, such as the development of CAR T treatments​, but one of the major hurdles has been to find a method to target solid tumours.

However, the team from Massachusettes Institute of Technology (MIT) have managed to discover one potential route to target solid tumours and found it to be effective in sending half of treated subjects into remission, in animal models.

Targeted cytokine delivery

Immune-stimulating drugs, called cytokines, are known to boost efficacy of T cells but need to be targeted in their delivery; if cytokines are infused throughout the body, the effect is not targeted and can lead to widespread inflammation.

The researchers were able to hone the delivery of cytokines by creating a nanoparticle than can hold cytokines, which can then be attached to T cells and is only loosed once a chemical change occurs on the surface of the T cell in the presence of a tumour.

Darrel Irvine, senior author of the study, explained to us the advantages of this means of delivery, allowing for “greater efficacy, by concentrating these drugs where they are needed, and greater safety, by lowering systemic exposure”​.

In the early-stage studies, 60% of the mice treated with this method of cytokine delivery were found to be tumour-free after multiple treatments.

In addition, the mice could receive eight times as much interleukin-15, a type of cytokine, without side-effects compared to injecting the drug throughout the body.

The possibilities for this type of potential treatment do not stop at cytokine delivery, Irvine outlined future work planned using the technology: “We remain interested in exploring other immunotherapeutic cargos beyond cytokines, that could promote other aspects of anti-tumour immunity, such as promoting immunogenic cell death of tumours or activation/recruitment of dendritic cells to tumours. Such stimulants could synergise strongly with adoptive T-cell therapy.”

For the moment, the current research will be taken forward by Torque Biotherapeutics, based in Massachusetts, which has licensed the technology and has, according to a spokesperson, established a manufacturing process for the particles.

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