Cancer Immunotherapy Could Be Transformed by Boosting Natural Killer Cells

Researchers at MIT and Harvard Medical School have developed a method to enhance natural killer cells that could transform cancer immunotherapy. The team engineered chimeric antigen receptor natural killer cells with modifications that prevent immune system rejection and improve their ability to destroy tumors. Early experiments in mice and laboratory human tissue show the enhanced cells are effective at fighting cancer and well tolerated, offering a promising foundation for next-generation treatments. 

Natural killer cells function as the body’s first defense against virus-infected or cancerous tissue. They react immediately to suspect cells without requiring activation or priming. Chimeric antigen receptors engineered onto NK cells extracted from patient blood enable the cells to target specific proteins that identify cancerous tissue more effectively. However, since producing sufficient engineered cells for treatment takes several weeks, scientists are exploring using healthy donor blood instead to create ready-to-deploy treatment stockpiles. 

The caveat is that using donor cells accelerates treatment availability but increases immune rejection risk. The research team identified specific immune cells that could attack transplanted treatment and made precise molecular changes to alter CAR-NK surface proteins. These modifications effectively hide transplanted cells from the host immune system while preserving their cancer-fighting capabilities. The protective modifications and cancer-fighting enhancements can be incorporated on a single DNA construct, making the production process significantly simpler. 

MIT biologist Jianzhu Chen explained that one-step engineering produces CAR-NK cells that avoid rejection by host T cells and other immune components while killing cancer cells more effectively and safely. Mouse experiments revealed notable differences between enhanced and standard versions. Modified CAR-NK cells persisted for at least three weeks while standard versions faced immune rejection within days, allowing cancer growth to continue unchecked in those control groups. 

The upgraded cells demonstrated an additional benefit beyond cancer-fighting improvements. They reduced the odds of developing a potentially fatal complication where the immune system triggers severe inflammation called cytokine release syndrome. This safety advantage addresses one of the significant concerns with current immunotherapy approaches that can provoke dangerous immune overreactions in some patients, sometimes requiring intensive care interventions. 

The findings could also boost CAR-T cell therapy efficacy, researchers say. Rather than using natural killer cells, this treatment employs ‘T’ immune cells. These treatments are effective for some patients but don’t work well in others. Subsequent clinical trials will be essential to determining whether positive laboratory and animal results translate to human patients. The researchers suggest their methods could apply to other cell-based products and support development of off-the-shelf allogeneic therapies for immediate deployment when patients need treatment. 

Many firms, such as Calidi Biotherapeutics Inc. (NYSE: CLDI), are also focused on developing new therapies aimed at boosting the way the immune system can effectively respond to cancer. These approaches include the use of oncolytic viruses. With time, many of these novel treatments could become commercialized and patients will access them. 

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