Tiny nanoparticles, far smaller than the width of a human hair, might help the body’s own immune system fight tumors, a new study shows. In experiments with mice, the nanoparticle-based therapy not only wiped out the original targeted breast cancer tumors, but metastases in other parts of the body as well. Human clinical trials with the new therapy could begin within the next several months, researchers say.
The search for drugs that spur the immune system to fight tumors is one of the hottest fields in cancer research. Immune sentries, known as T cells, are normally on the prowl for suspicious looking targets, 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 T cells’ alarm can be muted by so-called immune checkpoints, other proteins on the surface of normal cells that tamp down the immune response to prevent harmful autoimmune reaction to normal tissue. Tumor cells often over express these checkpoint molecules, putting the brakes on the immune system’s search and destroy work.
To overcome that problem, pharmaceutical companies have developed a number of different antibody proteins that block these overexpressed checkpoint molecules and enable the immune system to target tumors. In cases where there are lots of T cells in the vicinity of a tumor, or where tumor cells have undergone large numbers of mutations, which creates additional targets for immune sentries, T cells will signal a full-fledged immune response to the cancer. Such cancer immunotherapy can add extra years to patients’ lives.
However, existing cancer immunotherapy drugs work in only 20% to 30% of patients. In some cases, even when the checkpoint molecules are blocked that there are too few active T cells around to sound the immune alarm, says Jedd Wolchok, a cancer immunotherapy expert at the Memorial Sloan Kettering Cancer Center in New York City. In others, he says, tumors don’t display enough of the T cell’s targets, so-called tumor antigens, on their surface.
In August 2016, Lin and his colleagues reported in Nature Communications that when they injected a version of their nanoparticles into the bloodstream of mice with colon cancer along with a checkpoint antibody and blasted the tumors with light, the combination sparked the animals’ immune systems to destroy both the targeted colon cancer tumors as well as untreated tumors elsewhere. However, those particles also ferried a standard chemotherapeutic toxin to help kill the cancer cells. In their current study the researchers wanted to see whether the approach would work with just the immune response.
An artist’s conception of nanoparticles targeting tumor cells
This time Lin and his colleagues worked with mice with breast cancer, another form of cancer that often doesn’t respond to current immunotherapy drugs. Again, they injected the animals with their nanoparticles along with a checkpoint antibody. But this time their nanoparticles didn’t contain any additional chemotherapeutic drug. They then blasted the tumors with infrared light, and waited for the results. And in almost every case, not only was the primary breast cancer tumor destroyed, but metastases in the lung were wiped out as well, they report in the Journal of the American Chemical Society. “We were surprised to find that without the cytotoxic agents, you can achieve the same effect,” Lin says.
Original published by Science with sightly modification