Cancer-targeting treatment ‘steps on the accelerator’ to kill tumors
Many have heard of immunosuppressive drugs, which are a type of drug that suppresses the immune system, but lesser known are immunostimulatory drugs, which boost the body’s immune system. The latter is a potential solution for treating cancerous tumors, as the drugs prompt the immune system to attack the mutated cells. The problem? Ordinarily, these drugs could also cause the immune system to be overstimulated, attacking healthy cells with serious, sometimes fatal consequences.
That’s a problem the MIT researchers behind a new cancer immunotherapy study have solved. While introducing an immune-stimulating drug throughout the body can cause the immune system to attack healthy cells, the new delivery method detailed in Nature Biomedical Engineering is designed to specifically target cancerous tumors.
The method involves introducing IL-12, a type of stimulatory molecule, directly to where the tumor is – the team calls it “walking on gas”. This aspect of broader immunotherapy treatment is joined by another process that researchers describe as “letting go of the brakes,” at least when it comes to cancerous tumors and how they fight off the immune system.
While a healthy immune system is generally very good at clearing old, damaged cells and fighting infection, cancer cells – which have mutated genes – produce their own molecules that suppress the immune system’s ability to attack them. This reduces the body’s ability to fight and eliminate cancer cells, allowing them to grow and eventually spread to other parts of the body.
The researchers note that while this problem can be solved using existing drugs called checkpoint blockers, pharmaceuticals only work on certain types of cancer. However, combining these inhibitors with immune-boosting drugs may be more effective against resistant cancers, giving immune cells the boost they need to attack tumors.
It all comes down to the problem of unwanted side effects that come with boosting the immune system, including things as serious as organ failure, the researchers say. That’s where their job comes in – it’s about targeting the stimulatory molecules directly at the tumors, essentially telling the body to attack only those cancerous cells while leaving other healthy cells alone.
Work on the project has been ongoing for years, including a previous study by the team published in 2019 (via MIT) which involved targeting IL-12 molecules to cancerous tumors in mice. This new study is evaluating an improved way to bind IL-12 molecules and cytokines (immune cells) to tumors, by replacing the collagen-binding protein previously used with a compound called aluminum hydroxide (alum).
The alum particles are so small they are measured in microns, the researchers explain, noting that the small sizes mean the particles will stay where they were injected for several months. The study involved testing this potential immunotherapeutic treatment in mice, which were treated with a checkpoint blockade inhibitor and injected with IL-12. The results were promising.
The mice used for the study had three different types of cancer; treatment success in eliminating these tumors ranged from 50 to 90%. It should be noted that some of the mice had been injected with breast cancer cells which then spread to the lungs.
IL-12 treatment was found to clear tumors that had spread to the lungs, even though the injection was only given to the original tumor site. The results were less stunning when the injection was given without inhibitors, although the researchers say IL-12 with alum alone “showed some ability” to trigger the immune system against cancer cells.
As if that weren’t exciting enough, researchers say mice treated with this method of immunotherapy experienced none of the side effects that occur when IL-12 is introduced into the body without any means of targeting it. specifically tumors. What does this mean for human patients?
The inhibitor drug used in this treatment is already FDA-approved, the researchers say, and a startup has already licensed the technology. This startup, MIT Notes, will conduct his own study on alum-IL-12, and if he also finds favorable results, he will move on to additional tests that combine the immunostimulant and inhibitors.
It will still be some time before these immunotherapy treatments become a mainstream way to treat cancer and some other diseases, but this work represents a big step towards that future.