Researchers at the Weizmann Institute of Science in Rehovot developed a technique that significantly boosts the proliferation of T-cells — key players in the immune system’s defense — while maintaining, and in some cases even enhancing, their ability to kill cancer cells. This advancement addresses a major limitation of current cancer immunotherapies, where T-cells, despite multiplying in large numbers, often lose their cancer-fighting edge.

Cellular immunotherapy, one of the most promising treatments for cancer, 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 wage war on the cancer. Although this method has shown great potential, its success has been hindered by the fact that after rapid multiplication, T-cells tend to exhaust themselves, losing their potency.

Led by Prof. Benny Geiger from the Weizmann Institute’s Immunology and Regenerative Biology Department, a team of researchers developed what they described as a “synthetic immune niche” — an artificial molecular environment that enhances the performance of T-cells. This niche enables T-cells to reproduce more rapidly without diminishing their cancer-killing abilities.

This synthetic immune niche could be integrated into existing immunotherapy treatments to boost the effectiveness of T-cells, allowing doctors to use more potent cancer-fighting cells. By identifying optimal time windows for harvesting T-cells, doctors would be able to schedule treatments to maximize both the number of cells and their cancer-killing capacity.

Moreover, addressing the issue of T-cell exhaustion could extend the effectiveness of treatments, reducing the need for multiple rounds of therapy.

The breakthrough comes after years of research that Geiger began a decade ago alongside his colleague, Prof. Nir Friedman, who passed away in 2021. The synthetic immune niche consists of two carefully selected proteins inspired by the body’s natural immune system. This artificial environment accelerates T-cell proliferation while preserving, or even amplifying, their cancer-fighting strength.

In a study recently published in the peer-reviewed Journal for Immunotherapy of Cancer, Geiger’s team demonstrated that their synthetic immune niche could 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 the performance of T-cells,” said Geiger. “Our initial research managed to develop a niche of this kind, 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 external threats like cancer cells. However, they must first be activated to respond to the niche. 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 the cells’ receptors. The results revealed that the synthetic immune niche could significantly enhance the division rate of T-cells while preserving their effectiveness in killing cancer cells.

The team discovered that the T-cells’ functional abilities were tied to different activation windows. T-cells specifically triggered by cancer proteins typically lose their killing power about four days after activation. However, when exposed to the synthetic immune niche, these cells maintained their lethality even after rapid division.

In contrast, nonspecifically activated T-cells, which initially divided more slowly, experienced a temporary drop in their killing capacity, only to regain it on the seventh day after niche treatment.

By understanding these optimal time windows, the 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 significant implications for improving cellular immunotherapy, a treatment that, while promising, still faces limitations in its widespread applicability and effectiveness.

To measure the killing power of the T-cells, the researchers utilized time-lapse microscopy to document the interactions between immune cells and cancer cells. Their findings suggested an inverse relationship between rapid T-cell division and killing capacity — at least temporarily. However, the synthetic immune niche altered this dynamic, ultimately enhancing the T-cells’ cancer-fighting abilities at critical points.

The Weizmann team has patented the synthetic immune niche and begun testing its potential in human cells, in collaboration with Israeli hospitals and the MD Anderson Cancer Center in Houston. Early results are promising, with hopes that the technique could lead to more effective cancer treatments for patients who currently have few options.

“Cellular immunotherapy has shown incredible promise, but its effectiveness needs to be reinforced,” said Geiger. “Our immune niche can increase both the number of T-cells and their killing power. If it proves successful in humans, it could offer new hope for cancer patients around the world.”

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