Scientists at Yale have developed a method that assists the immune system in identifying and eliminating cancer cells that may be missed by other forms of immunotherapies.
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A distinct new immunotherapy
The ground-breaking new system could theoretically be used to target different types of cancer, and what’s important is that it offers an option of treatment for those cancers resistant to immunotherapy.
By their nature, cancer cells are good at avoiding detection, but in a paper published last month in the journal Nature Immunology, the system developed at Yale proves that it is successful at reducing and even eliminating melanoma and triple-negative breast and pancreatic tumors in mice.
The findings show that it was even successful in finding cancer cells located a distance from the primary tumor source. The Yale team presents a completely distinct new form of immunotherapy, one which can elicit a potent immune response against cancer.
Shortcomings of current immunotherapies
Immunotherapy is a biological therapy, it works by helping the body’s immune system to target and destroy cancer. It is often more targeted than conventional cancer treatments like chemotherapy and radiation, and severe side effects such as hair loss and nausea/vomiting are less likely with this kind of treatment.
However, while this kind of therapy has had the impact of revolutionizing cancer treatment, it is not perfect. Immunotherapy is not effective all the time. For some patients and some cancers, the treatment fails to identify the cancerous cells because of the molecular disguises they use. In not recognizing the cells, the therapy cannot work thoroughly.
The aim of the work at Yale was to address this flaw by creating an entirely new system by combining viral gene therapy with CRISPR gene-editing technology. The system, known as Multiplexed Activation of Endogenous Genes as Immunotherapy (MAEGI), works by searching for tens of thousands of cancer-related genes, and in finding them it marks their location and makes their presence more salient. Once marked, the cancer cells are targeted for immune destruction. The system was able to do this both for cancer cells at the main tumor site and for those at distances.
MAEGI assists the immune system in doing its job by helping them to locate the hard to find cancer cells. Once the cells are found the first time, with the help of MAEGI, the immune system is then able to recognize them again if they appear in the body later.
The problem other therapies have in spotting cancer cells is because, over time, the cells go through genetic changes. Studies have uncovered that as cancer cells genetically evolve, they can lose the ability to produce interleukin-33 (IL-33). When this disappears from the tumor, the immune system can no longer recognize the cells as cancerous, and therefore does not destroy it, allowing the cancer to spread. Research has uncovered this occurring in prostate, kidney, breast, lung, uterine, cervical, pancreatic and skin cancers. The new method will be able to detect cancer cells regardless of their ability to produce (IL-33).
Scientists are confident that the therapy could be used in the future to fight different types of cancer, as well as those that are difficult to treat with current immunotherapy. Future studies are planned to optimize the system, preparing it to be used in clinical trials with cancer patients. The system will need to go under vast amounts of clinical testing before it would be available as a treatment option. However, the first studies have given hope for the future development of an effective new treatment.
Wang, G., et al. (2019). Multiplexed activation of endogenous genes by CRISPRa elicits potent antitumor immunity. Nature Immunology. DOI: 10.1038/s41590-019-0500-4.