Body messenger improves cancer treatment | Karolinska Institute News

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The vesicles seem to make the tumor immunologically active, so that checkpoint therapy takes hold and can begin to work. These findings are further support for the further development of extracellular vesicles as a novel treatment modality against cancer, says the study’s final author Susan Gabrielsonprofessor at Department of Medicine, SolnaKarolinska Institutet.

Extracellular vesicles are sometimes called body bottle mail. They are nano-sized bubbles surrounded by membranes, which cells can transmit between themselves to exchange information. For example, vesicles from cancer cells can suppress the immune response and thus contribute to the spread of cancer, while vesicles from immune cells can trigger a reaction from the body’s immune system.

It can stimulate the cells of the immune system

In previous studies, KI researchers showed that a specific type of extracellular vesicle of immune cells can stimulate T cells of the immune system and reduce tumor growth in mice. In the current study, they examined how these vesicles function in a mouse model of melanoma that is insensitive to treatment with checkpoint inhibitors.

The extracellular vesicles in the study were isolated from mouse immune cells, namely dendritic cells. They are then supplied, in this case, with a cancer-specific protein called ovalbumin and a molecule called alpha-galactosylceramide, which then stimulate the immune system’s T cells and natural killer cells (natural killer cells).

When the researchers gave the follicles to mice in order to treat their tumors, or as a preventative measure before they began to develop tumors, the animals’ immune systems were activated with a strong T-cell response against the cancer protein. Activation did not occur if animals were given checkpoint inhibitors alone and was stronger when animals received a combination of vesicles and checkpoint treatment.

However, the researchers saw no effect on survival when the animals received a combination of vesicles and checkpoint inhibitors for therapeutic purposes, compared to vesicles alone. The researchers believe this may be due to the fact that the activated immune response did not have time to affect the tumors during the short period that the trial was underway. When the treatments were given to the mice prophylactically, giving a longer duration of action, survival was greater in the mice that received the combination than in the mice that received the vesicles only.

Tested on humans

As early as 2005, other researchers tested administering extracellular vesicles of human immune cells with the aim of treating cancer, and more clinical trials have since taken place. The vesicles were shown to be safe in these studies, but had only a small effect. Susan Gabrielson thinks this is because the experiments were done too early, before it was known what molecules the vesicles had to contain to be effective, something her group had worked a lot on. They are also trying to streamline the production of extracellular vesicles.

The goal is that we don’t have to take a patient’s own cells, but use cell lines instead. The vesicles can then be prepared in advance and frozen while the patient waits. We also believe that different types of treatment could be used for other forms of cancer and other diseases, says Susan Gabrielson.

The research was funded by the Swedish Research Council, the Cancer Foundation, the Radium Home research funds, the Stockholm Region, the Heart-Lung Foundation, and KID funds from the Karolinska Institutet. Susan Gabrielson holds a patent on B cell exosomes in immunotherapy and is part of the Scientific Advisory Committee for Anjarium Biosciences.

Publishing

Antigen-loaded extracellular vesicles induce response to anti-PD-1 and anti-PD-L1 treatment in a checkpoint refractory melanoma model.Roseanne E. Firman, Jozde Gokoler Akpinar, Animaryjn Offense, Loek Steiner, Pia Larsen, Andreas Lundqvist, Mikael CI Carlson and Suzanne Gabrielsson. cancer immunity research, Online Dec 22, 2022, doi: 10.1158/2326-6066.CIR-22-0540.