St. Joseph's College Jakhama
Small nanoparticles, much smaller than the width of a human hair, could help the body's own immune system fight tumors, a new study shows. In experiments with mice, nanoparticle-based therapy not only eliminated the original tumors of bad cancer, but also metastases in other parts of the body. The search for drugs that urge the immune system to fight tumors is one of the hottest fields in cancer research. Immune sentinels, known as T cells, are usually on the lookout for targets with a suspicious appearance, such as bacterial invaders and potential tumor cells. If they recognize one, they sound the alarm, inducing other immune cells to mount a larger response. However, the alarm of T cells can be silenced by so-called immune control points, other proteins on the surface of normal cells that compress the immune response to avoid harmful autoimmune reaction to normal tissue. Tumor cells often overexpress these checkpoint molecules, which slows the search for the immune system and destroys work.
To overcome this problem, pharmaceutical companies have developed a series of different antibody proteins that block these excess expressed point-of-control molecules and allow the immune system to attack tumors. In some cases where there are many T cells in the vicinity of a tumor, or where the tumor cells have suffered a large number of mutations, creating additional targets for immune sentinels, T cells will signal a complete immune response to the cancer. Such immunotherapy against cancer can add additional years to the lives of patients.
However, existing immunotherapy drugs against cancer work only in 20% to 30% of patients. In some cases, even when the control point molecules are blocked, there are very few active T cells to sound the immune alarm. But the tumors do not show enough targets of the T cells, called tumor antigens, on their surface.
But a seemingly unrelated conundrum offered the possibility of increasing the effectiveness of immunotherapy. Oncologists have long known that, in rare cases, after patients receive radiation therapy to reduce the size of a tumor, the immune system will generate an aggressive response that will eliminate not only the tumor, but metastasis throughout the body that is not They treated with radiation. Researchers now think that irradiation sometimes kills tumor cells in a way that exposes new antigens to T cells, preparing them to attack other tumor cells that also carry them.
Researchers are trying to use non-toxic nanoparticles to sensitize the immune system in a similar way. Getting the nanoparticles through the immune system is not easy. If they are too large, the cells in the blood called macrophages are swallowed. And the proteins of the blood tend to coat the particles, which facilitates their absorption. In recent years, the researcher devised a method to produce particles that are between 20 and 40 nanometers in size (a nanometer is one billionth of a meter), a range that can better bypbad macrophages. They also coated them with a shell of polyethylene glycol, which helps them survive longer in the bloodstream and enter the target cells. Finally, inside they incorporated powerful molecules that absorb light, based on chlorine, which convert nanoparticles into tumor killers.
In previous studies, the team discovered that once injected into the bloodstream, the particles can circulate enough to find their way in and around tumors. And because tumors often have a malformed and leaking vasculature, the particles tend to leak into the site of the cancerous tissue and are collected and internalized within the tumor cells. Once the nanoparticles are absorbed, the researchers shine near the infrared light on the tumors. That light is absorbed by chlorine-based molecules, which then excite nearby oxygen molecules, creating a highly reactive form of oxygen, known as singlet oxygen that tears away nearby biomolecules and kills the tumor cell. Singlet oxygen tends to tear tumor cells in a way that exposes many new tumor antigens to immune cells called dendritic cells, which, like the police that run a trawl, grab the antigens and present them to the T cells for an inspection closest. By doing so, they help the immune system to develop a powerful antitumor response even in cases where there are not many T cells nearby.
Recent report says that when a version of its nanoparticles was injected into the bloodstream of mice with colon cancer along with an antibody and destroyed the tumors with light, the combination elicited the immune system of the animals to destroy both tumors. colon cancer as well as tumors not treated elsewhere. However, those particles also transported a standard chemotherapeutic toxin to help kill the cancer cells. In their current study, the researchers wanted to see if the approach would work only with the immune response.
The researcher worked with mice with bad cancer, another form of cancer that often does not respond to current immunotherapy drugs. Again, they injected the animals with their nanoparticles together with a checkpoint antibody. But this time his nanoparticles did not contain any additional chemotherapeutic drugs. Then the tumors flew with infrared light and awaited the results. And in almost all cases, not only was the primary tumor of bad cancer destroyed, but lung metastases were also eliminated. They discovered that without the cytotoxic agents, they can achieve the same effect.
Researchers try to follow this method with human tests soon. With this cancer, immunotherapy can add additional years to the lives of patients.