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The new type of immunotherapy may eliminate all advanced tumor cells
The new type of immunotherapy may eliminate all advanced tumor cells. In recent years, there has been a new wave of cancer immunotherapy around the world, making this therapy gradually become the mainstream way of cancer treatment. As the key performer of the downstream effects of the immune response, macrophages play an important role in the immune response and have super “plasticity”.
Recently, researchers from Georgia State University published a groundbreaking study titled Intratumoral SIRPα-deficient macrophages activate tumor antigen-specific cytotoxic T cells under radiotherapy in Nature Communications, and developed a new type of immunotherapy based on macrophages. , Can effectively treat a variety of advanced cancers.
Macrophages are like scouts of the human body, they will swallow and destroy them when they encounter potential threats. However, cancer cells are very cunning. They often disguise themselves as normal cells and escape the immune surveillance of macrophages through the common selection mechanism that normal cells rely on to enhance their ability to divide, thereby suppressing the body’s immune response.
The culprit for this escape phenomenon of tumors is a receptor called “regulatory protein alpha (Sirpα)”, which is an inhibitory regulator of bone marrow leukocyte expression. Its typical function is to interact with the self-identifying marker CD47. The interaction to inhibit the function of phagocytes makes the tumor-killing immunity induced by radiotherapy (RT) severely restricted.
Therefore, in order to prevent macrophages from continuing to “injure the innocent”, the researchers developed a macrophage therapy based on Sirpα deficiency to combat cancer, and constructed an in vivo colon cancer model of MC38 for verification.
Studies have found that local radiotherapy and chemotherapy have cured colorectal cancer in Sirpα-deficient (Sirpα -/-) mice with advanced tumors, without obvious long-term adverse reactions, and can show a lifespan similar to that of healthy mice (about 18 month). This shows that macrophages knocked out of the Sirpα gene can initiate a powerful immune response against cancer by triggering inflammation and activating tumor-specific T cells, which can minimize the adverse effects on healthy cells.
In order to determine whether the long-term anti-tumor immunity in the treated Sirpα-deficient mice has been generated, the researchers performed tumor retransplantation experiments on Sirpα -/- mice from which colon cancer had been eradicated, and re-inoculated MC38 cells into the mice. . Surprisingly, cancer cells did not proliferate in mice. This indicates that the mice may have acquired long-term humoral anti-tumor immunity.
In addition, the researchers also found that when wild-type mice successfully inoculated with MC38 cells were injected with serum from Sirpα -/- mice from which tumors were eradicated, they could successfully inhibit the spread of cancer cells. This shows that the serum of Sirpα -/- mice from which tumors have been eradicated has the ability to prevent the formation of new tumors.
All in all, this study shows that Sirpα is the main manipulator of tumor microenvironmental immunity, and that this new technology combined with radiotherapy and chemotherapy may become a “pan-cancer therapy” that guides humans against all cancers.
So far, the treatment has been tested against the entire NCI-60 cancer portfolio, including 60 different human tumor cell lines, such as leukemia, melanoma, lung cancer, colon cancer, brain cancer, ovarian cancer, breast cancer, and prostate cancer. Cancer and kidney cancer, etc., and have been found to have significant effects.
Currently, researchers are applying to the U.S. Food and Drug Administration (FDA) for approval of the therapy as an investigational new drug, and plans to conduct human clinical trials in 2022. Not only that, this new treatment also received funding from the National Cancer Institute, Georgia Research Alliance, and Biolocity.
(source:internet, reference only)