Repositioning of mebendazole as an immunomodulator in cancer therapy

Time period:

1 January 2017 – 31 December 2019

Project leader:

Rolf Larsson

Project member:

Mårten Fryknäs, Peter Nygren

Funder:

Swedish Research Council

Type of award:

Project grant

Total funding:

3,000,000 SEK

We have previously identified the anti-parasitic drug mebendazole (MBZ) as a candidate for repositioning to cancer therapy and have observed clinical anti-tumor responses in patients resistant to standard therapy. We have also recently observed that MBZ induces a gene expression, surface marker and cytokine release patterns characteristic of a pro-inflammatory, anticancer M1 phenotype in monocyte and macrophage models. Based on these observations we now want to:1. Perform phase-1 and II clinical trials using a novel improved formulation of MBZ A pharmacokinetic (PK) study in healthy volunteers to evaluate the properties of our new MBZ formulation. Planned for Q3 2016. A proof of concept phase II clinical trial in 30+ patients with therapy refractory gastrointestinal carcinoma. The protocol will include PK monitoring and search for biomarkers  The trial will be performed at Dept of Oncology, Akademiska hospital, Uppsala. The trial is planned to start Q4 20162. Perform studies on the mechanism of action of MBZ induced monocyte/macrophage activation and tumor suppression.  3. Search for combination partners for inducing optimal immune activation (ex GM-CSF and interferon gamma).4. Synthesize and study structure activity relationship (SAR) studies using a focussed tailor-made library with MBZ analogues.5. Screening for repositioning candidates with immunomodulating activity using our in-house library dedicated for drug repositioning.