PhD-candidate The M-lab, Department Precision Medicine, School GROW, Faculty of Health, Medicine and Life Sciences

The use of immune modulating agents to “wake up” the immune system in patients is a remarkable breakthrough in cancer treatment. But despite their sophistication, only a minority of patients (e.g. 20% of melanoma and lung cancer) benefit from these new drugs. The causes of treatment failures are immensely complicated and multifactorial. Effective treatment depends on delivery of the correct combination of therapeutic agents at the malignant site, with minimal effect at healthy sites in the body. The proposed project aims to build on the proof-of-principle we established in earlier research: that tumor-colonizing Clostridium bacteria can continuously secrete high doses of biologically active therapeutics exclusively at the tumor site (Kubiak et al, Front Microbiol 2021). We hypothesise that the full potential of current immunotherapies can be realised through a more intelligent method of delivery to the tumour. Recombinant Clostridium, engineered to express genetically encoded therapeutics, will colonize solid tumors from where they will secrete cytokines and antibodies directly into the tumor micro-environment. Due to the precise nature of this “delivery vehicle”, the systemic toxic effects observed in all current immunotherapies will be prevented.

Using a translational approach, anti-tumor effects and activity and responsiveness of the immune system will be determined and modulated in relevant preclinical cancer models, upon systemic administration of recombinant non-pathogenic clostridial spores expressing a variety of therapeutic agents, alone and in combination with other treatment modalities. Through our results, we expect to demonstrate the superior therapeutic effect of delivering established immunotherapeutic agents to solid tumors with no negative effects on healthy tissues using recombinant Clostridium.

The research will be carried out within The M-lab, Department of Precision Medicine (GROW Research School, University Maastricht). The proposed work will be performed under the responsibility of Prof. Lambin, PI’s Dr. Theys and Dr. Dubois and senior researcher Dr. Bailey.

The team has extensive expertise in the field of oncology, radiotherapy, immunotherapy and

Clostridium with a proven track record. The experimental design, further execution of the proposed work and scientific reporting will be the responsibility of the candidate. He/she will directly supervise the animal technician and plan these experiments in close collaboration with him/her. Tight collaboration and scientific networking will enable to keep the community updated about our latest developments, to trigger interest in the novel combination approach, and to reach a global scientific audience.