“The new preclinical data show that nadunolimab reduces immune suppression and improves the anti-tumor effect of a cancer vaccine, further supporting the potential of nadunolimab. These data are also relevant in the context of our results from combination of nadunolimab with the immunotherapy pembrolizumab in the CIRIFOUR trial, as similar mechanisms likely control response to therapy in this setting as well. We look forward to continuing the fruitful collaboration with Professor Hanahan's group to better understand these effects, with the goal of providing new treatment options for patients with cancer,” said Göran Forsberg, CEO of Cantargia.

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.

“Immunotherapies have become a breakthrough in therapy of certain cancers, but as of today, these therapies are not curative and only benefit a minority of patients. It is imperative to understand the biological limitations to further improve the outcome, and these novel data provide new hypotheses for future clinical trials,” said Douglas Hanahan, Distinguished Scholar at the Ludwig Institute for Cancer Research.

These preclinical data are presented in detail in a poster session at the CRI-ENCI-AACR International Cancer Immunotherapy Conference 2023. More information on the poster session is found below:

Poster number: P225
Poster title: Pharmacological targeting of IL-1 signaling disrupts cancer-induced systemic immunosuppression and improves therapeutic vaccine response in HPV16-induced cancer
Session date and time: September 22, 2023, 12:45 – 2:00 PM CEST
Presenters: Lecointre Morgane and Jérémy Guillot

Nadunolimab is currently investigated clinically in pancreatic cancer, non-small cell lung cancer and triple-negative breast cancer, with over 200 patients treated to date. Positive interim data from nadunolimab in combination with chemotherapy indicate stronger efficacy than would be expected from chemotherapy alone. A clinical phase IIb trial in pancreatic cancer is currently in preparation.