Scientists propose extracting dendritic cells and priming them to fight cancer before returning them to a patient as part of a new immunotherapy approach. From the Ecole Polytechnique Fédérale de Lausanne (EPFL), researchers are looking to maximize current cancer immunotherapy methods to be powerful and very accurate.
A vital part of the immune system, dendritic cells are antigen-presenting cells, which means they identify, bind, and bring proteins unique to foreign invaders to show killer T cells. As their name suggests, killer T cells are the ones who destroy tumor cells.
“Dendritic cells acquire immunogenic antigens from the tumor and directly display them on their own surface," explained Michele De Palma.
The new technique focuses on improving the way dendritic cells recognize tumor antigens. Researchers extract dendritic cells from a cancer patient, which are exposed to tumor antigens and injected back into the patient. In theory, this process prepares dendritic cells so they are more equipped to find and present antigens in the patient so killer T cells can destroy the tumor. In the past, scientists have had trouble with tumor cells (and their antigens) evading detection by the immune system.
This approach isn’t perfect. The antigens exposed to dendritic cells after their extraction from the cancer patient are not identical to the antigens the dendritic cells actually come into contact with in the body. This variance increases the risk of killer T cells not being properly activated to kill tumor cells.
In the new study published in Nature Methods, EPFL researchers offer a solution: extracellular vesicle-internalizing receptors (EVIR). These are artificial receptors that help dendritic cells “selectively and efficiently” identify and bind tumor antigens in the body to present to killer T cells.
Scientists inject EVIRs into the dendritic cell, where they recognize exosomal proteins. These are small vesicles within the cell that, in the context of cancer, are released by tumors and are rich with tumor antigens. In past studies, exosomal proteins have been associated with promoting metastasis, the spreading of a tumor to various tissues.
EVIRs essentially introduce tumor antigens from exosomes to dendritic cells so they can better target them. Palma says that this is an “unconventional route for antigen presentation to T cells."
"The EVIR technology can intercept a natural phenomenon - the release of exosomes from tumors - to the patient's benefit," explained first author Mario Leonardo Squadrito. "It exploits pro-tumoral exosomes as selective nanocarriers of tumor antigens, making them available to the immune system for cancer recognition and rejection."
Scientists from the study plan on investigating the relationship between EVIRs, dendritic cells, antigens, and exosomal proteins further. Additionally studies will have to be done before the new immunotherapy approach can be applied as a cancer treatment.
Source: Ecole Polytechnique Fédérale de Lausanne
