A pioneering approach to cancer immunotherapy developed by Israeli researchers could greatly improve its effectiveness and expand treatment options for patients for whom conventional therapies have failed.
Researchers at the Weizmann Institute of Science in Rehovot have developed a technique that significantly increases the proliferation of T cells – key players in the immune system’s defenses – while maintaining, and in some cases even enhancing, their ability to kill cancer cells. The breakthrough addresses a major limitation of current cancer immunotherapies, where T cells, despite proliferating in large numbers, often lose their cancer-fighting advantage.
Cellular immunotherapy, one of the most promising cancer treatments, recruits the body's T cells to target and destroy cancer cells. In this process, T cells are extracted from the patient, activated, multiplied and reintroduced into the body to fight the cancer. Although this method has shown great potential, its success has been hampered by the fact that after rapid multiplication, T cells tend to become exhausted, losing their potency.
Led by Prof. Benny Geiger from the Weizmann Institute's Department of Immunology and Regenerative Biology, a team of researchers developed what they describe as a "synthetic immune site" – an artificial molecular environment that enhances the performance of T cells. This site enables T cells to reproduce more quickly without reducing their ability to kill cancer.
This synthetic immune site can be integrated into existing immunotherapy treatments to increase the effectiveness of T cells, allowing doctors to use more powerful cancer-fighting cells. By identifying the optimal time frame for T-cell recruitment, doctors will be able to plan treatments to maximize the number of cells and their ability to kill cancer.
Furthermore, addressing the issue of T-cell exhaustion may extend the effectiveness of treatments, reducing the need for multiple rounds of therapy.
The discovery comes after years of research that Geiger began a decade ago together with his colleague, Prof. Nir Friedman, who passed away in 2021. The synthetic immune site consists of two carefully selected proteins inspired by the body's natural immune system. This artificial environment accelerates the proliferation of T cells while maintaining, or even enhancing, their strength against cancer.
In a study recently published in the peer-reviewed journal Cancer Immunotherapy, Geiger's team showed that their synthetic immune patch can significantly improve the balance between T-cell proliferation and killing power.
“We were looking for a combination of natural immune system proteins that would help improve T-cell performance,” Geiger said. “Our initial research succeeded in developing a site of this type, but we didn’t fully understand the molecular mechanisms behind it until now.”
T cells act as the immune system's warriors, identifying and destroying foreign threats like cancer cells. However, they must first be activated. In the study, the researchers compared two methods of activating T cells: one using proteins derived from cancer cells and another using antibodies to bind to cell receptors. The results revealed that the synthetic immune zone could significantly increase the rate at which T cells divide while maintaining their effectiveness at killing cancer cells.
The team found that the functional capabilities of T cells were linked to different windows of activation. T cells specifically triggered by cancer proteins usually lose their killing power about four days after activation.
In contrast, nonspecifically activated T cells, which initially divided more slowly, experienced a temporary decline in their killing ability, only to regain it on day seven after warm treatment.
By understanding these optimal time windows, researchers believe they can fine-tune the use of T cells in cancer treatment, maximizing both their proliferation and their ability to destroy cancer cells. This discovery could have important implications for improving cellular immunotherapy, a treatment that, while promising, still faces limitations in its widespread application and effectiveness.
To measure the killing power of T cells, the researchers used time-lapse microscopy to document interactions between immune cells and cancer cells. Their findings suggested an inverse relationship between the rapid division of T cells and their killing ability—at least temporarily. However, the synthetic immune zone reversed this dynamic, ultimately enhancing the T cells’ ability to fight cancer at critical points.
Weizmann's team has patented the synthetic immunity space and started testing its potential in human cells, in collaboration with Israeli hospitals and the MD Anderson Cancer Center in Houston. Early results are promising, with the hope that the technique could lead to more effective cancer treatments for patients who currently have few options.
"Cellular immunotherapy has shown tremendous promise, but its effectiveness needs to be scaled up," Geiger said. "Our immune system can increase the number of T cells and their killing power. If successful in humans, it could offer new hope for cancer patients around the world."
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