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Cell: Engineered immune cells can target and inhibit cancer cell metastasis
Cell: Engineered immune cells can target and inhibit cancer cell metastasis. In a recent study, scientists genetically modified immune cells so that they can accurately transmit anti-cancer signals to organs that may spread cancer.
In the mouse model, the researchers found that the use of engineered cell therapy can effectively shrink tumors and prevent the cancer from spreading to other parts of the body. The research was led by scientists from the National Cancer Institute (NCI) under the National Institutes of Health (NIH) and was published in the journal Cell on March 24, 2021.
The author of the article, Dr. Rosandra Kaplan, NCI Cancer Research Center, said: “This is a novel immunotherapy that is expected to become a potential treatment for metastatic cancer.”
As we all know, metastatic cancer is difficult to treat. In this regard, Dr. Kaplan’s team has been exploring another method, that is, how to prevent the spread of cancer. Before the cancer spreads, it will send a signal to prepare the destination for the arrival of cancer.
In this new study, the NCI team explored the behavior of immune cells in the environment before cancer cells metastasize. Since Dr. Kaplan is a pediatric oncologist, the team mainly studied mouse models implanted with rhabdomyosarcoma, because rhabdomyosarcoma is a type of cancer that develops in the muscles of children and often spreads to the lungs.
To study the environmental information of the destination of tumor metastasis, the researchers looked at the lungs of mice after tumors formed in the muscles of the legs, but before the cancer metastasis was found in the lungs. NCI scientists discovered that the immune system has the natural ability to fight cancer, but this ability is significantly suppressed in the lungs.
Specifically, bone marrow cells are abundant in the niche before metastasis, and continue to gather there as the cancer develops. Bone marrow cells are responsible for the body’s initial response to infection, injury and cancer. When they detect a threat, they usually produce IL-12, which can warn and activate other immune cells. However, the researchers found that myeloid cells in the metastatic niche of the lungs would send out the opposite signal, suppressing the anti-cancer activity of immune cells.
Therefore, scientists want to know whether they can change the information transmitted by bone marrow cells to promote the immune system to play a role in the transfer target niche. Therefore, they used genetic engineering techniques to overexpress the IL-12 gene in the bone marrow cells of laboratory mice.
The study found that in mice with rhabdomyosarcoma, these genetically engineered myeloid cells (GEMys) produced IL-12 at the primary tumor and metastatic sites. The researchers found that, as hoped, GEMys recruited and activated immune cells that can kill cancer in the metastasis destination niche, and reduced the signal activity that suppresses the immune system.
Furthermore, the authors found that mice treated with GEMys cells had fewer metastatic cancers in the lungs and smaller tumors in the muscles. Compared with mice treated with unengineered bone marrow cells, mice in the GEMys group had a much longer lifespan. The researchers found similar results when studying mice with liver-spreading pancreatic tumors.
The NCI team also found that combined with chemotherapy, surgery or T cell transfer therapy, the effect of GEMy treatment was further improved. For example, two days after receiving chemotherapy, mice with rhabdomyosarcoma will be treated with GEMy again, which will completely eliminate the signs of cancer within 100 days.
In addition, evidence suggests that the combination of chemotherapy and GEMys can prevent cancer recurrence. When the researchers reintroduced the cancer cells into the mice cured by the combination therapy, tumors did not form. The researchers explained that this shows that the combination therapy can maintain the “immune memory” of cancer for a long time.
(source:internet, reference only)