Macrophages are a type of White blood cell specialized in detecting, phagocytizing (swallowing) and destroying foreign agents, such as viruses and bacteria. They are also responsible for stimulating the activity of other cells of the immune system and teach the body to remember and attack invading cells in the future. A group of scientists from the University of Pennsylvania have decided to take advantage of this learned immunity to design a kind of cancer vaccine using manipulated macrophages.
Cancer continues to be one of the most frequent diseases in the world; in fact, one in five people will develop some type of cancer throughout their lives, according to the International Agency for Research on Cancer (IARC), hence the importance of finding more effective therapeutic alternatives with fewer side effects. The solid tumors, such as breast, brain, or skinThey are especially difficult to treat. Surgery is usually the first option, but sometimes cancer cells remain behind that can mutate and spread to other organs and tissues.
Eliminating cancer from the inside using our own cells is the goal of researchers who have modified these white blood cells so that they are capable of remove solid tumors. The new therapy, which is explained in an article published in Nature Biomedical Engineering not only kills cancer cells, but also train the immune system so you can identify and kill them in the future.
A key therapy to design a future cancer vaccine
“Due to the physical properties of a solid tumor, it is challenging to design molecules that can enter these masses,” said Dennis Discher, Robert D. Bent Professor of Chemical and Biomolecular Engineering Elementary Mechanical Engineering and Applied Mechanics at the University of Pennsylvania , who adds: “Instead of creating a new molecule to do the job, we propose use cells that ‘eat’ invaders: macrophages”.
The engineered white blood cells were able to kill tumors in 80% of the mice and triggered an adaptive immune response.
“Macrophages recognize cancer cells as part of the body, not as invaders,” continues postdoctoral fellow Larry Dooling. “To allow these white blood cells see and attack cancer cells, we had to investigate the molecular pathway that controls cell-to-cell communication. Turning off this pathway: A checkpoint interaction between a protein called SIRPa in the macrophage and the CD47 protein found on all ‘self’ cells, was the key to creating this therapy.”
The researchers verified the functioning of their modified macrophages in “tumoroids” – conglomerates of mouse melanoma cells– in culture dishes and observed that macrophages organized themselves around cancer cells and cooperated to engulf them and destroy the tumor. when they tried live, these engineered white blood cells were able to kill tumors in 80% of the mice. In addition, removal of the tumor triggered an adaptive immune response, as weeks later, increased the immunoglobulin G antibody against cancer.
This engineered macrophage therapy works best in combination with available antibody therapy and may be the key to develop a cancer vaccinewhich kills cancer cells and teaches the body to kill cancer cells that appear later, which would be an advantageous change in strategy in the fight against cancer.