Solna [Sweden], Jan 1 (ANI): Extracellular vesicles, which are tiny membrane bubbles, appear to make tumors more susceptible to the immunotherapy drug known as checkpoint inhibitors and stimulate the immune system in mice. This is supported by a recent study from the Swedish Karolinska Institute published in Cancer Immunology Research.
A class of drugs known as a checkpoint inhibitor, which encourages the immune system’s T cells to attack cancer cells, has made significant progress in the treatment of many cancers in recent years.
Although some individuals respond quite well to treatment, a significant proportion see only minimal improvement. To improve cancer survival, researchers are putting a lot of effort into finding out why this is so and combining checkpoint inhibitors with other drugs.
A new cancer therapy Researchers from Karolinska Institutet now show that a form of round nanoparticles called exosomes or extracellular vesicles is a promising path to follow.
“It seems that the vesicles make the tumor immunologically active so that the checkpoint therapy can gain traction and start working,” says the study’s last author Susanne Gabrielsson, professor at the Department of Medicine (Solna), Karolinska Institutet. “These results lend support to the continued development of extracellular vesicles as a novel cancer therapy.” Extracellular vesicles are sometimes called the body’s messengers. They are nanoscale membrane-bound bubbles that cells can send to each other to exchange information. For example, vesicles from tumor cells can shut down the immune system so that cancer can spread, while vesicles from immune cells can activate an immune response.
Can activate immune cells In previous studies, KI researchers have shown that a certain type of extracellular vesicles from immune cells can activate immune T cells and reduce tumor growth in mice. In the current study, they investigated how these vesicles function in a mouse model of skin cancer that is resistant to checkpoint inhibitor therapy.
The extracellular vesicles used in the study were isolated from the mice’s own immune cells (dendritic cells). In this case, a cancer-specific protein called ovalbumin and a molecule called alpha-galactosylceramide, both of which stimulate T cells and natural killer cells, were then added.
When the vesicles were introduced into mice therapeutically to treat their tumors or prophylactically before their tumors began to develop, they activated their immune systems to produce a strong T-cell response to the cancer protein. The same effect was not achieved if the animals received only checkpoint inhibitors, and was most pronounced in animals receiving a combination of vesicles and checkpoint therapy.
However, the researchers observed no effect on survival when the animals received the combination vesicle-checkpoint treatment compared to vesicles alone, and believe that the duration of the experiment was possibly too short for the activated immune system to affect the tumors. When the treatments were given prophylactically to mice, which provides a longer duration of action, the mice that received the combination treatment showed greater survival than those that received only vesicles.
Tested on human patients Other researchers tried giving extracellular vesicles from immune cells to human patients as cancer therapy as early as 2005. In these studies, the vesicles have been shown to be safe but only minimally effective. Professor Gabrielsson believes it was because the experiments were done too early before the researchers knew what molecules the vesicles would contain to be effective, something her team has devoted a lot of work to. They also attempt to facilitate the production of extracellular vesicles.
“Our goal is to be able to use cell lines instead of having to take the patient’s own cells,” she says. “This will mean that the vesicles can be prepared in advance and frozen until needed. We also believe that variants of the treatment could be used for other forms of cancer and other diseases.” (ANI)