Solna [Sweden]: Extracellular vesicles, which are tiny membrane bubbles, appear to make tumours more susceptible to the immunotherapy medicine known as a checkpoint inhibitor and to stimulate the immune system in mice. This is supported by a recent study from the Swedish Karolinska Institutet published in Cancer Immunology Research. A class of medication known as a checkpoint inhibitor, which encourages the immune system's T cells to attack cancer cells, has made significant advancements in treating many cancers in recent years.
Even though some individuals respond to treatment quite well, a significant portion only sees minimal improvement. In order to improve cancer survival rates, researchers are putting a lot of effort into figuring out why this is the case and combining checkpoint inhibitors with other medicines.
A new cancer therapy: Researchers from Karolinska Institutet now show that a form of round nanoparticles called exosomes or extracellular vesicles are a promising path to follow. "It seems that the vesicles make the tumour immunologically active so that the checkpoint therapy can gain purchase and start to work," says the study's last author Susanne Gabrielsson, professor at the Department of Medicine (Solna), Karolinska Institutet. "These results give support to the further development of extracellular vesicles as a new cancer therapy."
Extracellular vesicles are sometimes referred to as the body's messengers. They are membrane-bound nano-scale bubbles that cells can send to each other to exchange information. Vesicles from tumour cells, for instance, can switch off the immune system so that cancer can spread, while vesicles from immune cells can activate an immune response.
Can activate immune cells: In earlier studies, KI researchers have shown that a certain type of extracellular vesicle from immune cells can activate immune T cells and reduce tumour growth in mice. In the present study, they examined how these vesicles function in a mouse model of skin cancer that is resistant to checkpoint inhibitor therapy.
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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 were then added, both of which stimulate T cells and natural killer cells.
When the vesicles were introduced into mice therapeutically to treat their tumours or prophylactically before their tumours started 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 were only given checkpoint inhibitors, and was most pronounced in animals that received a combination of vesicles and checkpoint therapy.
However, the researchers observed no effect on survival when the animals received the vesicle-checkpoint combination therapy compared with vesicles alone, and believe that the duration of the experiment was possibly too short for the activated immune system to affect the tumours. When the treatments were given prophylactically to mice, which gives a longer duration of action, the mice that received the combination treatment showed greater survival than those that only received vesicles.
Tested on human patients: Other researchers tried giving extracellular vesicles from immune cells to human patients as a cancer therapy already back in 2005. In these studies, the vesicles have proved safe but only minimally effective. Professor Gabrielsson believes that this was because the experiments were conducted too early before scientists knew what molecules the vesicles should contain to be effective, something to which her team has devoted considerable effort. They are also trying to simplify the manufacture of extracellular vesicles.
"Our aim 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)
