Trained immune cells raise prospect of universal cancer vaccine

Engineering immune cells to attack cancer is a form of treatment that is showing great promise, but it is complex because it involves extracting and modifying T cells before injecting them back into the body. Scientists have now demonstrated a way to not just arm immune cells while still inside the body, but equip them with the ability to fight any kind of cancer, providing an early proof-of-concept for a cheap, universal vaccine for the deadly disease.

Known as adoptive immunotherapy, the idea that our immune cells can be engineered to fight cancer has been explored by scientists since the 1980's. Some seriously encouraging advances have been made in the last few years, most recently through a trial involving patients with advanced blood cancer that yielded unprecedented response rates of more than 93 percent.

The technique works by harvesting the body's T cells, which play a central role in the immune response, and arming them with cancer-recognizing molecules through gene transfer. Known as chimeric antigen receptors, these molecules give the modified cells the ability to spot proteins on cancer cells once they are injected back into the body, at which point they latch on and start to kill them off.

While hugely promising, this method relies on the unique properties of blood cancer for the modified T cells to lock onto their target. Scientists have been unable to apply this approach to solid tumors where such clear markers aren't readily available, meaning the immune cells have trouble distinguishing healthy cells from cancerous ones.

But German scientists are now reporting an immunotherapy breakthrough that is significant in more ways than one. Led by Professor Ugur Sahin from Johannes Gutenberg University in Mainz, the team says it has worked out how to train immune calls in a way that is not only cheap and fast, but can be tuned to attack any type of cancer.

They begin with a snippet of the targeted cancer's genetic RNA code, which they encase in a fatty membrane. The scientists were able to give these particles, which they have dubbed RNA-LPX, a negative charge by fine-tuning the ratio of RNA to fatty membrane. Once injected into the bloodstream, this mild electrical charge guides the particles towards the body's dendritic immune cells, which are cells that specify targets for the immune system to attack.

Once they come together, the dendritic cells react to the RNA code to bring about the production of specific cancer antigens, which are molecules that brand a foreign invader as a threat so that other immune cells can get to work. This kickstarts an immune response and the production of a throng of T cells ready to take up the fight.

The scientists tested the new technology in three melanoma patients and mice, not with the aim of eliminating tumors but to establish whether they could steer the immune system in their direction. And they found that it did indeed induce a "profound" expansion of T cells, suggesting that the technique can help the body's defences catch some of the many cancers that slip through the net.

But perhaps the most promising aspect of this new technology is its versatility. "Virtually any tumor antigen can be encoded by RNA," the researchers write, meaning that so long as a tumor sample can be taken and a genetic profile can be created, the RNA-LPX particles can be programmed to fight virtually any kind of cancer.

With such a small sample size, there is clearly still some ways to go to prove its effectiveness and for a universal vaccine to enter clinical use. But evidence of an approach that stimulates an army of multi-cancer-fighting T cells that would otherwise lay dormant while being surrounded by the enemy is some exciting new territory.

The research paper was published in the journal Nature.

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