It has been known for some time, thanks to cancer research, that certain tumor cells can alter some specific macrophages. Subsequently, these bad macrophages contribute to the growth of a tumor. “Macrophages are cells that act as the vacuum cleaners of your immune system. Normally they trap and destroy invaders, but tumor cells hijack these cells to help them spread throughout the body,” explains Prof. Dr. Jai Prakash. Together with his team, he developed the new immunotherapy that turns these macrophages back into cells that fight tumors.
Nanoparticles for cancer control
Prakash’s team designed two nanoparticles with a diameter of 100 to 200 nanometers. Before those nanoparticles can start training the bad macrophages, they must first detect the bad macrophages. The aim of the research was to gain insight into and answer the question of how the nanoparticles can find the right location and macrophage.
Prakash and his team adapted the nanoparticles for this. These consist of a double layer of specific fats (phospholipids), so-called nanoliposomes. They have long tails that prefer to stick together in the double layer. “We replaced some of the nanoliposomes with variants with a slightly shorter and charged tail that occasionally flips outwards. We call that ‘tail-flipping’,” says Prakash. The flipped tails that are created in this way are recognized by the bad macrophages and then the entire particle is eaten, the scientists discovered.
With that knowledge it was clear how the bad macrophages could be tackled. That was when the training of the immune cells to fight cancer started. This training ensures that they can be used to fight tumors again. To do this, the researchers added a small component of the cell wall of a bacterium to the ‘tail-flipping’ nanoliposomes in the double-layer wall of these nanoparticles.
Previous research has already shown that these small pieces of bacterial wall can train macrophages. “The bad macrophages take up these molecules. By bringing this drug to the bad macrophages in this way, we prevent them from being recognized by the wrong cells. This prevents damage to other parts of the body,” explains Prakash.
Prevent metastases
The publication describes that the retrained hijacked macrophages are able to inhibit tumor growth. In tests in mice with breast cancer, this resulted in a 70 percent reduction in tumor growth and the spread of tumor cells – so-called metastases – was prevented. For example, the trained macrophages prevented tumor cells from ‘preparing’ lung tissue to receive tumor cells. The latter is the process that precedes metastasis. Due to the action of the trained macrophages, the tumor cells that reached the lungs no longer led to the formation of a new tumor.
The publication, ‘Cancer immune therapy using engineered ‘tail-flipping’ nanoliposomes targeting alternatively activated macrophages’, is freely accessible to everyone. Prof. dr. Dr. Jai Prakash is a pharmacist and an entrepreneurial scientist in the Advanced Organ Bioengineering and Therapeutics research group (Faculty of Applied Sciences, TechMed Center).