Developing the next generation bacterial cancer therapy
The vision of T3 Pharmaceuticals is to improve the lives of cancer patients with highly innovative treatments. Despite significant advances of classical therapies, there remains a high need for novel and innovative medicines to treat cancer. T3 Pharmaceuticals is dedicated to fill this gap by developing highly specific and efficient treatments using live bacteria.
HeLa cells (nuclei in blue) were treated with a control strain (left) or a strain delivering a protein (green, right).
Cell biological research is often hampered by the lack of appropriate methods that allow the fast, synchronized and efficient delivery of proteins into eukaryotic cells. The most widely used technique is DNA transfection ultimately leading to expression of the desired protein. This results in a heterogeneous and unsynchronized cell population after an incubation time of 12-48 hours. Hence, the protein under study is often present for far longer than physiologically relevant or desirable. Despite these drawbacks, DNA transfection is considered the standard technique for protein expression.
Bacteria as a protein delivery system
T3 Pharma (T3P), financed by the Commission for Technology and Innovation (CTI), the Swiss Cancer League (SCL) and additional foundations, has developed an innovative technique matching the above mentioned needs, that is further suited for combination with Omics and allows for biochemical experiments. The method, which was first established in the lab of Prof. Cécile Arrieumerlou at the Biozentrum Basel, is based on a bacterial protein delivery nanomachine: the type 3 secretion system (T3SS) encoded by several Gram-negative bacteria. The system delivers bacterial proteins – so-called effectors – directly into eukaryotic host cells. A genetically engineered bacterial strain, which is deprived of all endogenous effectors, was obtained from Prof. Guy Cornelis, one of the discoverers of the T3SS, and serves as the basis for translocating only the proteins of choice into the eukaryotic cells. This system offers distinct advantages: protein delivery is fast, synchronized, homogenous and efficient. Furthermore, our tool can be applied to almost all available cell lines with consistent performance.
Wide range of applications
The advantages of the T3P-technology make it attractive for various applications. In combination with proteomics one can for example study protein interactions or signaling dynamics. The convenient combination with mass spectrometry allows studying the impact of a protein at a systems level. The fast and synchronous delivery further enables researchers to introduce their protein of interest in a timed fashion. This allows studying short-lived signaling events and signaling kinetics or the impact of a protein during different stages of the cell cycle. Furthermore, the function of toxic proteins can be investigated. Due to its wide range of applications, the ease of use and the cost efficiency, T3P-technology is already successfully applied at the Biozentrum and within international collaborations. The technology has been published in The Journal for Cell Biology: “A bacterial type III secretion-based protein delivery tool for broad applications in cell biology” (Ittig et al. 211 (4): 913, JCB, 2015).
Proprietary vehicle to target solid tumors
Besides many potential applications in research use, protein delivery in vivo holds great therapeutic potential. The well-known bacterial preference to replicate at the site of solid tumors allows us to employ the bacteria as vehicle for delivery of therapeutic proteins into tumor cells. T3 Pharmaceuticals has developed and optimized a proprietary bacterial vehicle that has a strong preference to accumulate in solid tumors when administered from a distal site. At the site of the tumor, the bacteria are able to multiply while in healthy tissue they are cleared by the immune system. The accumulation of bacteria in tumor tissue in combination with the efficient delivery of therapeutic proteins forms the basis for the next generation cancer therapy.
Further information: T3 Pharmaceuticals