Nanoparticles awaken immune cells to fight cancer

Robert F. Service in Science:

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. But a seemingly unrelated puzzle offered the prospect of boosting immunotherapy’s effectiveness. Oncologists have long known that in rare cases, after patients receive radiation therapy to shrink a tumor, the immune system will mount an aggressive response that wipes out not only the tumor, but metastases throughout the body that hadn’t been treated with the radiation. Researchers now think that irradiation sometimes kills tumor cells in a manner that exposes new antigens to T cells, priming them to target other tumor cells that carry them as well, says Wenbin Lin, a chemist at the University of Chicago in Illinois, and one of the authors of the current study.

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