Scientists explore new ideas for improving cancer immunotherapy

Melanoma
New research seeks to improve the success rate of immunotherapy treatments for melanoma and other cancers.

The big story in oncology over the past few years has been the rise of immunotherapy, including drugs that improve the ability of the immune system to recognize and attack cancer. As promising as these treatments are, some patients don’t respond as well as others, prompting a major effort in the oncology community to uncover the causes of immunotherapy resistance and search for solutions to the problem.

New research suggests that one emerging pathway known as Hippo may play an important role in subduing cancer immunity. In particular, it’s kinases LATS1/2 in that pathway that may be problematic, the scientists found. The research was led by the University of California at San Diego and published in the journal Cell.

Improper signaling along the Hippo pathway contributes to cancer development, according to a press release from UCSD, and studies have shown that a loss of LATS1/2 enzymes promotes cancer cell survival and proliferation. So the UCSD team was surprised to discover that when they deleted LATS1/2 from mouse cancer cells, the ability to stimulate an immune response that ultimately destroyed the cancer actually improved.

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Further studies are needed to determine if the human immune response mirrors that of the mouse, but if it does, combining a LATS1/2 inhibitor with a checkpoint inhibitor may help patients who don’t otherwise respond to immunotherapy drugs, said Toshiro Moroishi, the lead author of the study. “LATS is an ideal target because there are many kinase inhibitors that have been successfully developed as cancer drugs," he said in the release.

Separately, researchers in Switzerland, working alongside Novartis, looked into Interleukin-2 (IL-2) in immuno-oncology. As promising as the treatment is for advanced cancer, it’s also problematic, because it stimulates the production of regulatory T cells, which suppress the ability of the immune system to attack tumors, they write in the journal Science Translational Medicine.

So they developed an IL-2 antibody called NARA1. It blocks CD25, a unit of the IL-2 receptor, which in turn prevents regulatory T cells from interrupting the immune response.

When they combined IL-2 and NARA1 and tested it in mice with metastatic melanoma, they doubled progression-free survival, the researchers wrote in the paper. Although a humanized form of NARA1 still needs to be developed, they suggested that further study of the interaction between it and IL-2 should be planned as a potentially effective treatment for melanoma and other cancers.