Cantargia reported new preclinical data highlighting how nadunolimab, an IL1RAP-targeting antibody currently in phase II clinical development, can be used to block the activity of cancer-promoting immune cells and increase the anti-tumor efficacy of immunotherapy i.e. a cancer vaccine. The data were generated by Professor Douglas Hanahan's research group at the Lausanne Branch of the Ludwig Institute for Cancer Research and the Swiss Institute for Experimental Cancer Research (EPFL) and are presented in a poster session at the CRI-ENCI-AACR International Cancer Immunotherapy Conference 2023. Tumors possess a wide variety of strategies by which they can gain resistance to anti-tumor therapies.

One such strategy is the expansion of immune cell populations known as myeloid-derived suppressor cells (MDSC). MDSC have immunosuppressive properties and can mediate resistance to immunotherapy, as well as chemotherapy and cancer vaccines. The new data demonstrate that IL-1 signaling molecules, including IL-1alpha, drive the in vivo expansion of MDSC which have high levels of IL1RAP, the target of nadunolimab.

Nadunolimab can potently block signaling via IL-1alpha and IL-1beta. In a model of cervical cancer, shown to produce IL- 1 signaling molecules and trigger MDSC expansion, a nadunolimab surrogate was able to dampen the MDSC expansion and reduce tumor growth. Notably, the nadunolimab surrogate also improved the anti-tumor efficacy of a cancer vaccine, in parallel with increasing the number of tumor-reactive T cells generated in response to the vaccine.

Thus, nadunolimab can alleviate immunosuppressive mechanisms used by tumors to provide resistance against anti-tumor therapies. These preclinical data are presented in detail in a poster session at the CRI-ENCI-AACR International Cancer Immunotherapy Conference 2023.