This is the appearance of a tumor after MIT researchers delivered a protein that binds aluminum hydroxide to cytokine (IL-12) to the tumor. Pink color represents IL-12 and yellow color is aluminum hydroxide. When IL-12 attached to the tumor activates the immune cells (T cells) around the tumor, the immune cells attack the cancer cells and cure. Provided by MIT.
Immune anticancer drugs, called third-generation cancer treatments, work by activating the body’s immune system so that immune cells attack cancer cells. Unlike the first-generation chemotherapy or second-generation targeted anti-cancer drugs, it was expected to reduce the side effects of anti-cancer drugs and maximize the therapeutic effect, but conquering cancer still has a long way to go. This is because, when the immune system is excessively activated with immuno-cancer drugs, there is a side effect of immune disease symptoms in which immune cells attack not only cancer cells but also normal cells.
Scientists are continuing research on immune anticancer drugs that do not attack normal cells while maximizing the effect of activating immune cells. Researchers at the Massachusetts Institute of Technology (MIT) in the US have developed a method to directly deliver a protein that efficiently stimulates immune cells to target cancer cells while suppressing the symptoms of immune disease that appear when immunotherapy is administered. It was released on the 10th (local time). In Korea, researchers at the Korea Institute of Science and Technology (KIST) are conducting research to reduce the side effects of immune anticancer drugs and increase their effectiveness, such as developing nanoparticles that effectively activate immune cells.
● Reduce side effects by controlling ‘cytokines’ and increase anticancer effect
Using drugs that stimulate the immune system can activate immune cells, but fatal side effects such as inflammatory ‘cytokines’ caused by overactivation of immune cells are a hindrance.
Cytokines are glycoproteins used as signaling substances to control and stimulate the body’s immune system. It is secreted from macrophages, which are immune cells, and T lymphocytes, a type of white blood cell, and plays a role in activating T cells that attack cancer cells. ‘Interleukin’ and ‘interferon’ are representative cytokine proteins.
A research team led by Darrell Irvine, deputy director of the MIT Cork Institute for Integrated Cancer Research, is studying how to reduce side effects by controlling the cytokine ‘Interleukin-12 (IL-12)’. In a 2019 study, we succeeded in attaching the IL-12 protein to the collagen-binding protein and delivering it directly to the tumor. The principle is that the collagen binding protein is attached to the collagen commonly found on the surface of the tumor, and IL-12 also binds to the tumor at the same time. In this way, the inflammatory response caused by overactivation of immune cells is reduced and only T cells on the surface of the tumor are activated to enhance the anticancer treatment effect.
In this study, the researchers developed a method to replace the collagen-binding protein with aluminum hydroxide so that the cytokines bind more strongly to the tumor. Aluminum hydroxide is often used as an adjuvant to increase the immune response of vaccines. As a result of administering the immunotherapy using this method to mice with cancer, it was found that 50 to 90% of the tumor was removed.
Vice President Irvine said, “Delivering the cytokine IL-12 directly to the tumor can be applied not only to immune anticancer drugs, but also to vaccines and therapeutics that stimulate the immune system. We plan to start clinical trials within the next few days.”
● Techniques that cannot avoid immune cells are emerging one after another
Tumors secrete substances that neutralize surrounding immune cells, including T cells, which are representative immune cells, depending on the degree of development. It grows while weakening the immune system, like hiding one’s identity behind immune cells. For this reason, immunotherapy has a limitation in showing efficacy only in some cancer patients.
Insan Kim, senior researcher at KIST, developed nanoparticles that effectively activate immune cells in various cancer types in 2020. The research team focused on ‘exosomes’ to overcome the limitations of immuno-cancer drugs that are only effective for some cancer patients. Exosomes are nanometer-sized particles released by cells that play an important role in processes such as blood clotting, cell-to-cell signaling, and waste management.
The research team used exosomes to make immune cells recognize cancer as an ‘enemy’. In experiments using exosome nanoparticles, anticancer effects were confirmed in various tumor models such as breast and colorectal cancer. The research team explained, “Exosomes specifically fuse with acidic cancer cells to create a target signal on the surface of cancer cells.”
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