Extracellular vesicles may improve immunotherapy

A new study by researchers at the Karolinska Institute (KI) demonstrates how extracellular vesicles (EVs) activate the immune system of mice and appear to sensitize
their tumors to checkpoint inhibitors.

"EVs are important mediators of cell-to-cell communication and potential candidates for cancer immunotherapy
," the researchers wrote.
"Immune checkpoint blockade, particularly the PD-1/PD-L1 axis, can alleviate T cell failure, but is only effective
in a subset of cancer patients.
Causes of treatment resistance include low activation of cancer antigens by primary T cells, poor antigen provision, and reduction
of T cell infiltration into tumors.
As a result, combinatorial strategies have been extensively explored
.
Here, we investigated whether EV treatment can induce susceptibility to anti-PD-1 or -PD-L1 therapy in a checkpoint-refractory B16 melanoma model
.
”

Dr Susanne Gabrielsson, the last author of the study and professor at the Karolinska Institutet (Solna), said: "It seems that these vesicles make the tumour immunoactive, so checkpoint therapy can be purchased and get to work
.
" "These results support the further development of extracellular vesicles as a new cancer therapy
.
"

In earlier studies, KI researchers have shown that certain types of extracellular vesicles from immune cells can activate immune T cells and reduce tumor growth
in mice.

In the current study, the researchers examined the function of these vesicles in a mouse model of
skin cancer resistant to checkpoint inhibitor treatment.

When vesicles were introduced into mice to treat tumors or for prevention before tumors began to develop, they activated the immune system, creating a strong T cell response
to cancer proteins.
The same effect could not be achieved if only checkpoint inhibitors were given, and the effect was most pronounced
in animals receiving combined vesicles and checkpoints.

When mice were given prophylactic treatment, the duration of action was longer, and mice receiving combination therapy showed greater survival rates
than mice treated with vesicles alone.

"Our goal is to be able to use cell lines, rather than having to extract the patient's own cells
," she says.
"This means that the vesicles can be prepared in advance and frozen when
needed.
We also believe that this variant of treatment can be used for other forms of cancer and other diseases
.
”