For many types of cancer, survival rates have increased dramatically -- but there's still plenty of room for improvement. Now, researchers are trying to expand tailored therapies that work for some types of tumors on other types of tumors as well.
Part of the reason why cancer is so dangerous is that it "hides" itself from the body's immune system. If you can get the body to recognize the tumors, you have a very strong ally in defeating cancer. This is where CAR T-cell therapy comes in.
CAR T-cell (Chimeric Antigen Receptor T-cell) therapy is a highly specialized form of immunotherapy and one of the more promising avenues against cancer. The process involves extracting immune cells (T cells) from a patient and modifying them. Specifically, the cells are modified so that they can recognize and target specific molecules on tumors.
The challenge is making sure the T cells can recognize the cancerous cells and attack them, while at the same time leaving healthy cells intact. For instance, CAR-T cell therapy against some forms of leukemia and lymphoma target a molecule CD19, which is present on tumor cells. But CD19 is not present, however, in acute myeloid leukemia (AML) cells.
So researchers have to find other molecule candidates, but it's kind of like finding a needle in the haystack.
Two research teams led by Professor Sebastian Kobold together with Dr. Adrian Gottschlich from LMU Munich have used AI algorithms to scan 25,000 potential cell surface molecules. Ultimately, they zoomed in on two promising molecules.
“Such an analysis would not have been possible a few years ago, since the required single-cell data has been generated only very recently,” says Dr. Carsten Marr, who led the AI-assisted analysis part of the study at Helmholtz Munich, in a statement for LMU Munich.
The resulting CAR-T cells were then tested on different cells, including cells from AML patients. The results are very promising: “Not only are these CAR-T cells effective against AML, they also destroy hardly any healthy cells,” says Kobold.
The next step is to figure out good manufacturing practices (GMP) through which these cells can be produced at a larger scale. When GMP manufacturing is achieved, researchers can move on with clinical trials. Kobold expects the first tests to take place in the next 2-3 years.
Meanwhile, another approach was proposed by Professor Marion Subklewe, and colleagues also at LMU Munich. They worked on a way to target a molecule called CD33 -- and then switch.
The reason is that CD33 is present in many other, non-cancerous cells of the body, which makes side effects severe. This new approach would make customizable CAR-T cells that can switch functions.
“This allows us to manage and control the therapy much better than before," says Subklewe. "We can repeatedly turn it on and off again and we can design and structure treatments in a more individualized fashion. Because we can steer the CAR T-cells to several molecules on tumor cells, we expect that this will produce a stronger and broader immune response against the cancer. By replacing the adapter, we alter the tumor specificity and the approach can therefore be easily transferred to other types of cancer – including solid tumors such as bowel or lung cancer.”
As exciting as this type of treatment is, current approaches are limited to a small number of patients per year. Finding out ways to scale the treatment is also essential if we are to truly tackle cancer.
The future of cancer treatment holds promise. As breakthroughs in immunotherapy and other technologies converge, they enhance our capacity to outsmart this formidable disease. Researchers are optimistic about the road ahead, as the therapeutic landscape evolves and paves the way for new possibilities in cancer treatment. Although scaling challenges still remain, these developments offer hope for improved survival rates and a better quality of life for patients across the globe.
