The Aryl Hydrocarbon Receptor (AHR) as a Driver of Cancer Immunosuppression
Hercules Pharmaceuticals, a Dutch biopharmaceutical company developing innovative anti-cancer drugs will present a poster, Poster LB-128, at the AACR meeting in Chicago on Monday April 16, 2018, from 8:00am-12:00pm, Poster section 45. The poster will be presented by, amongst others, Prof. David Sherr, co-founder of Hercules and international key opinion leader in the field of cancer immunology at Boston University.
The results presented show that the Aryl Hydrocarbon Receptor (AhR) is an important driver of cancer and cancer immuno suppression and that AhR inhibition could have powerful anti-cancer effects. Acting downstream of IDO inhibitors, Hercules’ AhR inhibitor HP163 promise to be more effective in blocking the tryptophan>IDO/TDO>kynurenine>AhR pathway.
The crucial role of AhR in cancer was demonstrated in a syngeneic murine cancer model, where animals received cancer cells from which the AhR was removed by Crispr Cas. Absence of AhR in tumor cells completely blocked tumor growth.
Where AhR knock-down shows the maximum achievable effect of AhR inhibition, Hercules’ AhR inhibitor HP163 already demonstrates better tumor growth reduction than IDO inhibitor epacadostat in a syngeneic murine colon cancer model.
It is Hercules’ aim to develop AhR inhibitors that have single agent efficacy in cancer patients. Furthermore, there is good scientific rationale for combining AhR inhibitors with other anticancer approaches, like anti PD-1/L1 antibodies and IDO inhibitors.