Personalized dendritic cell vaccines have continued to show success with the treatment of certain cancers.
Dendritic cell vaccines are increasingly showing success in the treatment of certain cancers. Dendritic cells are antigen-presenting cells that process antigens then present them to T cells. In the personalized approach to using dendritic cells vaccines, cells are obtained from the patient, exposed or loaded with cancer antigens, and grown. The resulting antigen-loaded dendritic cells are injected back into the patient, where the dendritic cells can elicit the anti-cancer immune response of T cells.
Although the development of dendritic cell vaccines can have very promising utility in cancer treatment, the efficiency is still in need of improvement. Modifying dendritic cells so that they may recognize cancer cell-specific extracellular vesicles (EVs) can improve dendritic cell presentation of antigens to T cells. Extracellular vesicles such as exosomes are produced by cells in general; however, those derived from tumors are associated with various processes involved with cell-cell interaction affecting metastasis, but they can also deliver antigens to dendritic cells.
A group of researchers from the Swiss Institute for Experimental Cancer Research designed a chimeric receptor that gives dendritic cells the ability to specifically recognize tumor EVs. The lentivirus-encoded chimeric receptor, called EV-internalizing receptor (EVIR), is capable of the selective uptake of cancer cell−derived EVs by dendritic cells. Their research showed that the EVIR enhances the presentation of tumor EVs containing various tumor antigens to T cells by dendritic cells.
The resulting increase in the dendritic cells’ efficiency in antigen presentation bolsters a patient’s T cell response to a tumor. The main mechanisms by which this is possible involves cross dressing, the transfer of already formed MHCI complexes from the surface of infected cells directly to dendritic cells without further antigen processing. Another mechanism involves the recycling of MHCI between the intracellular compartment and the cell surface. Study results showed that vaccination of mice with the EVIR dendritic cells inhibited tumor growth more efficiently than vaccination with control dendritic cells (those designed with a nonfunctional EVIR). Vaccination with EVIR dendritic cells may be a tool to improve T cell anti-tumor responses and address cancer-related immunosuppression.