Doctors & scientists reveal ‘natural cancer killer’
In this DML Report…
Scientists at Harvard Medical School and the Massachusetts Institute of Technology have engineered a new type of chimeric antigen receptor natural killer (CAR-NK) cells designed to target and destroy cancer cells while evading rejection by the patient's immune system. These cells build on the existing CAR-T therapy, which modifies T cells to attack specific cancers but carries risks of severe side effects like cytokine release syndrome (CRS) that can lead to multi-organ failure. In contrast, the modified CAR-NK cells silence the expression of HLA class 1 proteins on their surface using short interfering RNA (siRNA), preventing detection and attack by host T cells. This approach addresses a key limitation of standard CAR-NK cells, which often deplete rapidly due to immune rejection. The research focuses on lymphoma, a blood cancer affecting the lymphatic system that impacts about 90,000 Americans annually and results in 20,000 deaths each year.
The study involved implanting mice with human-like immune systems and lymphoma-causing cells to simulate the disease. Researchers then injected these mice with the modified CAR-NK cells, which persisted in the body for three weeks and nearly eliminated the tumors. In comparison, mice treated with unmodified natural killer (NK) cells or standard CAR-NK cells saw those therapies deplete within two weeks, allowing the cancer to progress unchecked. NK cells, inherently part of the immune system, kill invaders without prior training, and the CAR modification equips them to recognize cancer-specific proteins. The engineering process required only one additional genetic step beyond standard CAR insertion, enhancing the cells' tumor-killing efficiency. Jianzhu Chen, the senior study author and a professor of biology at MIT, stated: "This enables us to do one-step engineering of CAR-NK cells that can avoid rejection by host T cells and other immune cells. And, they kill cancer cells better and they’re safer."
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Published in Nature Communications, the findings suggest modified CAR-NK cells could enable "off-the-shelf" therapies, producible in advance without patient-specific customization, unlike traditional CAR-NK or CAR-T cells that require weeks of replication from a patient's blood sample. This could accelerate treatment upon diagnosis and reduce CRS risks compared to CAR-T therapy. The Boston-based team anticipates adapting these modifications for ongoing clinical trials targeting lymphoma and other cancers. Additionally, they are collaborating with a biotech company to test CAR-NK cells for lupus, an autoimmune disorder affecting 1.5 million Americans where the immune system attacks healthy tissues. Chen indicated that these cells may eventually supplant CAR-T therapy entirely.