'Cross-dressing' cells may improve cancer treatment

Swiss researchers have designed a groundbreaking technique that uses artificial receptors to enhance the body's immune response to tumors.

Cancer treatments are constantly evolving; one of the more recent shifts in treatment revolves around enhancing the natural immune response.

Our immune system is excellent at destroying and removing damaged, faulty, or old cells, but in the case of cancer, it tends to need a little help.

Immunotherapies are designed to stimulate a patient's immune system to fight the cancer within. Although the latest immunotherapies can be effective, they only work for the minority of patients who have solid tumors.

The race is on to enhance these methods and make them work for a wider range of patients. Involved in this push is a group from Ecole Polytechnique Federale de Lausanne (EPFL), Switzerland.

Dendritic cell vaccines

Specifically, the Swiss group is interested in improving so-called dendritic cell vaccines. Dendritic cells — also referred to as antigen-presenting cells — are an important part of the immune system. They capture antigens from foreign bodies and hand them over to killer T cells, which then neutralize the threat.

To create dendritic cell vaccines, dendritic cells are removed from the patient and "force-fed" tumor antigens before being released back into the patient. In this way, killer T cells are primed to destroy tumor cells, which are normally experts at evading the immune system.

Dendritic cell vaccines have already shown promise, but they do have limitations. One major drawback is that the tumor antigens used to "feed" the dendritic cells are from lab-grown tumors, not the patient's own. Because each tumor is different, the vaccine is not exactly matched and, therefore, may only be partially activated by the resident tumor.

A new advance

The researchers from EPFL, led by Prof. Michele De Palma, have gone some way toward fixing this problem.

Two images of EVIR-engineered dendritic cells (green) capturing tumor antigens in exosomes (gold/red). The cell nuclei are blue.
Image credit: C. Cianciaruso/M. De Palma/EPFL

They created artificial receptors, known as extracellular vesicle-internalizing receptors (EVIRs).

Dendritic cells are extracted from a patient and EVIRs are inserted into them.

When the dendritic cells are returned to the patient's body, they are primed to recognize types of small vesicle called exosomes.

Exosomes are tiny packages that transport various molecules between cells; important in a number of processes, such as coagulation, cell signaling, and waste management, they are produced by tumors in large amounts. In cancer cells, they are thought to play a role in metastasis, helping cancer travel to, and thrive in, distant parts of the body.

EVIRs trap exosomes traveling through the body, giving dendritic cells the exact blueprint of the resident tumor. The dendritic cells can then inform the killer T cells and boost the patient's immune response to the cancer.

Using imaging techniques, the team demonstrated that EVIRs enhanced transfer of tumor antigens from the exosome to the outer membrane of the dendritic cell.

Their results are published this week in the journal Nature Methods.

"We call this phenomenon cross-dressing, which alludes to the fact that the dendritic cells acquire immunogenic antigens from the tumor and directly display them on their own surface. 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."

Prof. Michele De Palma

The team hopes that this new technology will eventually improve immunotherapy's specificity and killing power. Mario Leonardo Squadrito, first author of the study, explains:

"The EVIR technology can intercept a natural phenomenon — the release of exosomes from tumors — to the patient's benefit. It exploits pro-tumoral exosomes as selective nanocarriers of tumor antigens, making them available to the immune system for cancer recognition and rejection."

Before this groundbreaking technology can be used in patients, it will need more study. The authors are planning to continue this line of inquiry alongside scientists from CHUV University Hospital of Lausanne.