Boosting cancer therapy with refined dendritic vaccines

22 Jan 2018
Boosting cancer therapy with refined dendritic vaccines

Researchers and physicians are looking into ways of increasing the precision and strength of the immune attack on a tumour.

One approach is the "dendritic cell vaccine".

Dendritic cells are specialized immune cells whose role is to capture antigens from foreign bodies and present them to the immune system's killer T cells, which will then attack and destroy the invaders.

For the vaccine, dendritic cells are taken out of the patient, "force-fed" with tumour antigens, and finally re-injected back into the patient.

The idea is to facilitate the ability of the dendritic cells to prime killer T cells against the tumour, which is notoriously skilled in concealing itself from the patient's immune system.

Dendritic cell vaccines have achieved some clinical success but not without several limitations.

For example, the tumour antigens used to "feed" the dendritic cells are generally not taken from the patient's tumour but from lab-grown cancer cells that are only partially similar to those of the patient.

This can limit the power of the vaccine because its tumour antigens may differ from those of the patient's tumour, meaning that the killer T cells would not be properly activated to recognize and attack the tumour.

A group of researchers led by Michele De Palma at EPFL have now created artificial receptors called EVIR (extracellular vesicle-internalizing receptors), which enable the dendritic cells in the vaccine to selectively and efficiently capture antigens from the actual patient's tumour. 

This is achieved by inserting the EVIR into the dendritic cell, where it recognizes a protein on small vesicles called exosomes.

Their findings are published in Nature Methods.

Exosomes are profusely released by the tumour and contain a variety of tumour antigens.

They are also increasingly implicated in the promotion of metastasis and other processes that may facilitate the growth and spreading of cancer.

By capturing exosomes coming from tumours, the EVIR helps the dendritic cells to precisely acquire tumour antigens from the cancer cells.

The dendritic cells then present these antigens more efficiently to killer T cells, thus amplifying the patient's immune response against their tumour.

Imaging techniques also revealed that EVIRs promote the direct transfer of tumour antigens from the exosome surface to the outer membrane of the dendritic cell.

"We call this phenomenon cross-dressing, which alludes to the fact that the dendritic cells acquire immunogenic antigens from the tumour and directly display them on their own surface," says Michele De Palma. "This is a fascinating and unconventional route for antigen presentation to T cells, which does not require complex and rate-limiting molecular interactions inside the dendritic cell."

The study opens up new avenues for developing more sophisticated and potent cancer immunotherapies.

"The EVIR technology can intercept a natural phenomenon - the release of exosomes from tumours - to the patient's benefit," says Mario Leonardo Squadrito, first author of the study. "It exploits pro-tumoral exosomes as selective nanocarriers of tumour antigens, making them available to the immune system for cancer recognition and rejection."

Although the new technology has the potential to increase the efficacy and specificity of dendritic cell vaccines, further pre-clinical work is required before it can be translated into a cancer treatment.

"We are currently exploring potential clinical applications of our technology together with colleagues at the CHUV University Hospital of Lausanne," says De Palma.

Source: Ecole Polytechnique Fédérale de Lausanne