The immune system is capable of identifying and attacking cancer cells in the body. This process depends on the tumor producing damaged RNA, which then sticks to cell surfaces and provides the antigens that the body identifies as foreign and therefore targets. However, a natural mechanism within the body that removes faulty RNA ironically aids many cancers to avoid detection and therefore limit immune system responses to the disease.
Now, a new preclinical study has found that targeting and blocking this clean-up mechanism can allow cancer antigens to express on tumor cells and allow the immune system to quickly identify and attack them.
The study was conducted by a University College London team and was published in the journal Immunity. The study focused on a quality-control mechanism in cells referred to as NMD (nonsense-mediated mRNA decay). The job of this cellular mechanism is to identify and destroy defective genetic messages so that proper cellular function and replication is maintained. Healthy cells have this pathway, and so do cancer cells.
The researchers, led by Doctor Roberto Vendramin, wanted to find out whether targeting this pathway could improve the way the immune system works against cancer. Their view was that the NMD process results in too few cancer antigens being expressed on tumor cells, thereby making it harder for immune cells to find and kill off those malignant cells.
The team blocked the NMD pathway in lab tissues so that tumors could make defective proteins using the faulty RNA messages. Those defective proteins were then broken down and formed antigens, which were expressed on the surface of cancer cells. This increased the quantity of identifiers that the immune system could detect and launch an attack against the cancer cells.
The researchers argue that this method has the potential to boost the effectiveness of immunotherapy, especially in people that have exhibited limited responsiveness to these therapies. Even those that are responding can have improved treatment outcomes if the damaged RNA clean-up process is blocked in cancer cells.
This was an early study, and it could take several years for the method to be developed further and fine-tuned for testing in clinical trials. The researchers estimate that in about half a decade, treatments targeting the NMD mechanism may have advanced to the level of getting regulatory approval for use in treating patients. Dr. Vendramin says this approach has the potential to be used as a standalone treatment or alongside other immunotherapies indicated for cancer.
It would be interesting to hear what entities like Calidi Biotherapeutics Inc. (NYSE American: CLDI) in the cancer immunotherapy field think about the roadblocks that this promising approach may have to navigate before reaching the bedside of patients.
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