“These very exciting data by Dr Merad’s group show how IL1RAP can be targeted to disrupt tumor-promoting and treatment-resisting networks in the tumor microenvironment, thereby opening up for new treatment opportunities that engage the immune system” said David Liberg , CSO of Cantargia. 

CRC is the third most common cancer and the second leading cause of cancer-related death worldwide. MSS CRC accounts for over 90% of metastatic CRC cases and is one of the most challenging solid tumors to treat with immune-checkpoint inhibitors targeting the PD-1 pathway, most likely due to alternative immunosuppressive mechanisms.

The new preclinical results further indicate that IL1RAP dependent signaling is part of an immunosuppressive axis within both the primary tumor and metastatic sites. This involves tumor cells, fibroblasts and myeloid cells within the tumor microenvironment (TME). Treatment with a nadunolimab surrogate antibody counteracted the immunosuppressive TME and expanded the cytotoxic T cell compartment, thereby opening for immunotherapy combinations. Combining the nadunolimab surrogate antibody with anti-PD-1 immune-checkpoint inhibitors showed a synergistic effect by reducing tumor burden in a CRC model that is otherwise unresponsive to immunotherapy. Disruption of this immune suppressive axis presents a unique opportunity to overcome resistance to immunotherapy, which has the potential to transform outcomes for metastatic MSS CRC patients.

The results was shared in an oral presentation by Dr. Jesse Boumelha from Icahn School of Medicine at the Keystone conference Cancer Immunotherapy: Basic Mechanism Informing Clinical Applications & combinations in Québec Canada on March 17^th.