New immunotherapy strengthens immune cells in the fight against cancer tumors

The Immune System's David vs. Cancer's Goliath

What looks here like an amoeba or a slug crawling along is a deadly enemy – a cancer cell. The much smaller, round immune cell seems powerless against it. But a new immunotherapy could help. It combines an antibody and an inhibitor in such a way that it mobilizes the T-cells of the immune system against cancer – and renders them immune to the cancer's counter-measures.

An immune cell attacking a much larger cancer cell. © M. Oeggerli/ Micronaut 2019, M. P. Trefny and A. Zippelius, Translational Oncology, University Hospital Basel/ University of Basel

Our immune system is actually well equipped to recognize and eliminate foreign, diseased, and cancerous cells. But in the case of cancer, these weapons of our immune system often fail. Cancer cells develop a camouflage that hides them from the immune cells. In addition, they release inhibitors that specifically disable the T-cells of the immune system.

T-cell versus tumor cell

The image above shows such a T-cell attacking a cancer cell. In the scanning electron microscope, the two "opponents" are clearly distinguishable: While the cancer cell, with its flat shape and cell protrusions, resembles a crawling amoeba, the T-cell is much smaller and more compact. It almost seems like David against the much larger Goliath.

But the immune cell has help:

Immunotherapies for cancer now help protect our T-cells against the tumor cells' defense strategies and mobilize them against cancer. This is possible with antibodies that block specific receptors on the T-cells, thus preventing the inhibitors released by the tumor from binding. The messenger molecule interleukin-2 was also used in cancer therapy as an immune activator some 40 years ago. However, immunotherapies also have side effects and are not effective against every type of cancer.

Combination drug boosts immune cells

Researchers have now developed a new immunotherapy that combines two strategies: The active ingredient is a fusion molecule consisting of a variant of interleukin-2 and an antibody. This fusion offers two advantages: The antibody binds to and blocks a specific receptor on the T cell. At the same time, it delivers the interleukin-2 directly to the target cell, where it can exert its full effect: stimulating the immune cell to attack the tumor.

"The tumor normally suppresses the immune system, but the fusion molecule overcomes this suppression and additionally activates the immune cells," explains lead author Clara Serger of the University of Basel. Tests with lung cancer cells showed that the combination therapy can even reactivate exhausted immune cells. Because the interleukin-2 is delivered directly to its target cell, its effect is limited to these T cells. It does not affect other, inhibitory immune cells, as the team reports.

Serger and her colleagues hope that this new combination drug will enable a more efficient and gentler immunotherapy. A first phase 1 clinical trial is already underway.

Science Translational Medicine, 2025; doi: 10.1126/scitranslmed.adr3718

Source: University of Basel