- New form of immunotherapy wherein dendritic cells are made to
acquire and present tumor antigens on their surface could make
immunotherapy more effective and precise
- Immunotherapy, a form of cancer treatment that aims to stimulate
the patient's immune system is currently effective only in some patients
with solid tumors.
dendritic cells, in other words, making them acquire and present tumor antigens
on their surface could make immunotherapy for solid tumors more effective,
according to a group of scientists at École Polytechnique
Fédérale de Lausanne (EPFL).
Dendritic Cells Acquire Tumor Antigens - EVIR Technology
- Aiming to make immunotherapy more precise and effective
in solid tumors, the research team created
artificial receptors called EVIRs (extracellular vesicle internalizing
receptors) to be incorporated in the dendritic
- These EVIRs are inserted into the dendritic cells (a type of immune
- These EVIR-incorporated
dendritic cells are injected into the patient as a "dendritic cell vaccine".
- The EVIRs in the dendritic cell are capable of recognizing vesicular
structures called exosomes that
are released abundantly by patient's tumor cells. These exosomes carry on their surface various tumor
antigens and are also believed to promote tumor growth and metastases.
- The EVIRs efficiently capture the exosomes released by tumor and
transfer them on to the surface of dendritic cells, thus facilitating
cross-dressing and tumor antigen presentation on the surface of dendritic
- The tumor antigens on the dendritic cells are then presented in a more
effective manner to the host T-cells (a type of immune cell) boosting
the patient's immune response to his cancer.
- Imaging techniques have shown that EVIRs aid the direct transfer of tumor
antigens from the exosomes to the outer membrane of the dendritic cell.
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," says
Michele De Palma, who led the
research at EPFL. "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."
Version of Dendritic Vaccines - Limitations
- Dendritic cells
are specialized immune cells
capable of capturing antigens from exogenous agents and presenting to
the host T cells, which will then attack and destroy the foreign agent.
- To create the dendritic vaccine,
dendritic cells removed from the patient, are "force-fed" with tumor antigens, and re-injected back into
- It was expected that these dendritic cell vaccines would improve
the ability of T-cells to destroy the tumor cells that have evolved
the art of "hiding" from the immune T-cells of the host.
cell vaccines have attained limited clinical success but do have several
is because the tumor antigens used to "feed" the dendritic cells
are obtained from lab-grown cancer
cells and not taken from the patient's tumor.
- These lab grown tumor cells are only partially similar to those of the
patient's tumor cells and thus limit the power of the vaccine because
the killer T cells will not be properly stimulated to recognize and kill
the tumor cells.
The current study opens up new avenues of
research to find novel and more effective forms of immunotherapy.
‘Displaying tumor antigens on the surface of dendritic cells improves immune destruction of tumor cells by stimulating host T cell immunity against the cancer.’
"The EVIR technology can intercept a
natural phenomenon - the release of exosomes from tumors - to the patient's
benefit," says Mario Leonardo Squadrito, first author of the study.
"It exploits pro-tumoral exosomes as selective nanocarriers of tumor
antigens, making them available to the immune system for cancer recognition and
In conclusion, following the promising
results of this study, further preclinical trials would still be required
before it can be ready to be used on patients. "We are currently exploring potential
clinical applications of our technology together with colleagues at the CHUV
University Hospital of Lausanne," says De Palma.
- Mario Leonardo Squadrito, Chiara Cianciaruso, Sarah K Hansen, Michele De Palma. EVIR: chimeric receptors that enhance dendritic cell cross-dressing with tumor antigens. Nature Methods, (2018); DOI: 10.1038/nmeth.4579