Our immune systems have evolved an impressive arsenal of molecules that target and destroy tumours. Now, Darrell Irvine at the Massachusetts Institute of Technology and colleagues have found a way to upgrade this native artillery.

Immune cells called cytotoxic T-cells swarm over and demolish cancerous cells inside the body. Unfortunately, many tumours emit a mysterious chemical cocktail to weaken any T-cells that swim too close.

While investigating how to increase T-cells’ ability to attack tumours, Irvine’s team found they could fasten 100 nanoparticle capsules to a single T-cell without impairing its function – capsules they could fill with any number of drugs.

The team injected these tooled-up T-cells into mice with tumours – and the T-cells made a beeline for the tumours. Nanoparticle capsules released loose into the mice’s bloodstream were destroyed by the spleen and liver, however.


Send in the interleukins

Next, Irvine’s team filled the nanoparticle capsules with interleukins – molecules naturally produced by the immune system that give T-cells chemical encouragement to keep on fighting. When they injected these into mice with bone and lung cancer, the T-cells not only swarmed over the tumours but stayed active far longer than T-cells with empty capsules.

What’s more, mice injected with unmodified T-cells died from their tumours within 30 days, whereas mice that received T-cells armed with interleukin were still alive and improving in health a month later.

Previous clinical trials have used simultaneous injections of T-cells and interleukins, but massive doses of interleukins throughout the body can be toxic. “Instead of bathing the whole body in interleukins, we found a way to focus the action of the drugs only on the T-cells,” says Irvine.

“Darrell’s work is really interesting,” says Aaron Foster at the Baylor College of Medicine in Houston, Texas. “The use of nanoparticles really simplifies the modification of T-cells because you don’t have to change them genetically. That could really speed up some of the clinical trials.

“Another drawback of gene therapy techniques is the cost and complexity. Darrell uses a more chemical-based methodology that has equivalent or similar effects and might be a lot cheaper in the end.”

Journal reference: Nature Medicine, DOI: 10.1038/nm.2198