Targeting AhR: A Promising New Approach to Cancer Immunotherapy
How an oral inhibitor may have the potential to reactivate the immune system and tackle tumor growth.
It infiltrates, learns, adapts and grows. Cancer is a clever disease that has pushed the limits of medicine – and the human body – for centuries. Current estimates show that there will be 27.5 million new cases of cancer each year by 2040.1
Typically, when an infection strikes the body, our immune system deploys T cells to target and destroy invading pathogens. T cells are also deployed to destroy abnormal, malfunctioning cells such as cancer cells. But cancer stays one step ahead, using mechanisms to hide and sending mixed signals to avoid an attack. Less than a decade ago, first-generation immunotherapies, called immune checkpoint inhibitors (ICIs), delivered a major breakthrough in cancer therapy. Targeting a pathway that cancer uses to suppress the immune system, ICIs can reactivate the body’s defense with significantly improved outcomes for a subset of patients with a broad variety of cancers, even in the metastatic setting.
For most, however, the effects are not realized: roughly 70% of patients with various tumors do not respond to ICI treatment. Cancer seems to have found yet more ways to out-smart the immune system. But now, Bayer is targeting what appears to be a key player in orchestrating immune escape: the aryl hydrocarbon receptor (AhR).
Expert insights: immunity through innovation
Dr. Ilona Gutcher, Group Leader Immuno-Oncology Research at Bayer, is the leading research pharmacology expert on the AhR. She reveals, “More and more research suggests that the AhR, once activated, triggers events that suppress immune responses and promote tumor progression. The AhR appears to be a central mediator in the whole process, so inhibiting it may reactivate immune responses and provide a new therapeutic strategy for patients with cancer."
As part of a strategic research collaboration between Bayer and Michael Platten’s group at the German Cancer Research Center (DKFZ), scientists have developed a selective AhR inhibitor that is now being tested in a clinical trial in patients with advanced solid cancers.
The AhR inhibitor is intending a powerful double-act on the immune system. Firstly, to reinvigorate the immune response by stimulating the activity and function of cytotoxic T cells and dendritic cells, the latter resulting in activation of even more T cells. Secondly, to decrease immune suppressive processes by blocking the function of regulatory T cells and suppressive myeloid cells.