DEVELOPMENT OF ANTITUMOR DENDRITIC CELL VACCINES WITH ALDH1A2 INHIBITORS TO OVERCOME IMMUNE SUPPRESSION

Abstract

Vaccines based on dendritic cells have traditionally been considered an exciting field of research in personalized treatment for cancer patients; however, their efficiency has usually been hindered by the same conditions under which the vaccine must be effective. In particular, the tumor microenvironment can be thought of as a hostile area which can disable immune system cells. However, recent discoveries have revealed a definite mechanism that can explain this effect: specifically, the ALDH1A2-retinoic acid (RA) axis. One can describe this process as brakes that prevent dendritic cells from fully maturing. For example, when such cells are isolated from the body and cultured in vitro using common growth factors, a high level of ALDH1A2 may be produced. It is responsible for the synthesis of retinoic acid, which causes the body to produce regulatory T cells, or the peacekeeper cells, rather than the necessary soldier cells required for fighting the tumor. However, to overcome this problem, scientists have started developing the next generation of vaccines along with the use of strong ALDH1A2 inhibitors. With the inhibition of this enzyme, we could essentially release the brake of the immune system. The research shows that with the absence of this signal through the production of retinoic acid, the dendritic cells will once again regain their function, resulting in an extremely aggressive attack on the tumor by CD8+ cytotoxic T cells. By inhibiting the immune suppression caused by the tumor, the inhibitors will enable the vaccine to work more effectively.