The M-Lab is a basic science and translational research laboratory. The vision of The M-Lab is to translate basic research findings into clinical research aimed at improving cancer diagnosis and treatment. The strategic focus is two fold
Research Line 1 : targeting the tumour microenvironment
Research Line 2 : Clostridium mediated Therapy
Research Line 1
Research Line 2
Research Line 1
Research Line 2
Targeting the tumour microenvironment with hypoxia activated prodrugs and/or immunotherapies in particular immunocytokines. For example we have shown that the combination of immunotherapy, in particular immunocytokines and radiotherapy, yielding a synergistic treatment with a systemic and memory effect (watch the animation). This antibody-based immunotherapy is currently further exploited in the combination with hypoxia targeting drugs, in order to battle the hypoxic immunosanctuary (watch the animation), the topic of his ERC advanced grant. We also have published and unpublished data demonstrating that Hypoxi Activated Prodrugs have a huge potential in particular if the right patient is selected with two type of biomarkers: hypoxia biomakesr and homologous recombination biomarkers. Hypoxia-Activated-Prodrugs (HAPs, see https://youtu.be/1sidMh5ZF70 ) are specifically activated in hypoxic environments and can improve response when combined with treatments such as immunotherapy. For example he novel HAP CP-506 is only activated under hypoxic conditions (less then 0/2% oxygen). The potency of CP-506 has already been proven in preclinical studies, especially in tumours with Fanconi Anaemia (FAN) and homologous recombination (HR) mutations or in combination with immunotherapy.
Clostridium mediated Therapy. These anaerobic bacteria specifically thrive in necrotic tumor areas but are also part of our microbiome. Our group established that from these anaerobic bacteria, Clostridium sporogenes and Clostridium Bytyricum have best clinically applicable characteristics (non-pathogenic, high sporulation capacity, tumor-specific). Currently initial steps in translating this finding into an applicable clinically relevant tool (imaging/drug-delivery) are ongoing
Clostridium species are a crucial component of the healthy human gut. Members of this genus have been shown to assist colonocyte metabolism, induce regulatory T cells - especially as multi-species communities - and produce neuroprotective antioxidants (Figure 2). They are one of the two numerically predominant genera of the human gut. Their ability to produce spores not only allows them to cross the gastric acid barrier after oral consumption, it also renders the shelf-life of probiotics a non-issue. Clostridial spores are immensely robust, with the capacity to survive extreme temperatures, radiation and desiccation, while retaining the ability to restore active growth almost indefinitely.
Over the past 10 years, researchers have made a quantum leap in there development of molecular tools to study clostridia. Using CRISPR-Cas9 and its variants, the deletion or addition, up- or down-regulation of nearly any DNA sequence in the bacterial genome has become possible. This opens the way for chromosomal expression of reporter systems and exogenous products (e.g. cytokines such as IL15, chemokines, antigens…) without the disadvantage of antibiotic markers that can be transferred to other gut inhabitants or into the environment.
The M-Lab utilises a CRISPR-Cas9 gene editing vector for the addition or deletion of sequences to/from the bacterial chromosome in a range of Clostridium species. My team was instrumental in the application of CRISPR-Cas9 technology to engineer Clostridium sporogenes to secrete biologically active IL-2, and was previously involved in creation of the Clostridium-Directed Enzyme Prodrug Therapy (CDEPT) (11, 12). This uniquely engineered strain will serve as a platform to further exploit other immune modulators in this species and others.
Clostridium species are a crucial component of the healthy human gut. Members of this genus have been shown to assist colonocyte metabolism, induce regulatory T cells - especially as multi-species communities - and produce neuroprotective antioxidants (Figure 2). They are one of the two numerically predominant genera of the human gut. Their ability to produce spores not only allows them to cross the gastric acid barrier after oral consumption, it also renders the shelf-life of probiotics a non-issue. Clostridial spores are immensely robust, with the capacity to survive extreme temperatures, radiation and desiccation, while retaining the ability to restore active growth almost indefinitely.
Over the past 10 years, researchers have made a quantum leap in there development of molecular tools to study clostridia. Using CRISPR-Cas9 and its variants, the deletion or addition, up- or down-regulation of nearly any DNA sequence in the bacterial genome has become possible. This opens the way for chromosomal expression of reporter systems and exogenous products (e.g. cytokines such as IL15, chemokines, antigens…) without the disadvantage of antibiotic markers that can be transferred to other gut inhabitants or into the environment.
The M-Lab utilises a CRISPR-Cas9 gene editing vector for the addition or deletion of sequences to/from the bacterial chromosome in a range of Clostridium species. My team was instrumental in the application of CRISPR-Cas9 technology to engineer Clostridium sporogenes to secrete biologically active IL-2, and was previously involved in creation of the Clostridium-Directed Enzyme Prodrug Therapy (CDEPT) (11, 12). This uniquely engineered strain will serve as a platform to further exploit other immune modulators in this species and others.