A major challenge in cancer therapy is to develop treatments that only impact the cancer but not the healthy tissue. In order to avoid side effects, it is thus important to distinguish cancer cells from healthy cells. Unfortunately this discrimination is inherently difficult to achieve as cancer cells originate from the patients’ once healthy cells. A classical approach is to use antibodies that have the capacity to recognize patterns only present on cancer cells. Yet, this requires that these tumor-specific patterns are known. Currently this is only the case for a limited number of tumor types.
With T3 Pharmaceuticals we have developed a vehicle that is highly specific for solid tumors without the need to know tumor-specific patterns. It was more than 100 years ago when German doctors have made the observation that patients suffering from cancer can benefit from bacterial infections. Since then, various bacteria have been found to grow specifically in solid tumors. Using modern tools, we have genetically modified such bacteria to further increase their natural specificity for solid tumors. Importantly, this high specificity is based on general features of solid tumors and does not require a detailed understanding of the tumor type.
Within the frame of the project supported by the Gebert Rüf Stiftung, these bacteria will now be further modified in order to optimally attack cancer cells:
On the one hand, we will engineer bacteria to be good catalyzers for the conversion of a non-toxic substance into a highly toxic substance. As the bacteria are only present in the tumor the cell-toxic product will only be generated nearby tumor cells but nowhere else in the body. This would allow administering a non-toxic substance to a patient, which will then only be converted by the bacteria waiting in the tumor into its toxic form.
Secondly, we have developed a technology allowing the delivery of proteins produced by bacteria directly into cancer cells. This is reached with a bacterial nano-machine, best described as injection needles at the periphery of bacteria. Like a gun, bacteria use this machine to shoot proteins into cells. Here, we will employ this bacterial weapon, but arm it with selected protein “bullets” having a therapeutic impact on cancer cells.
What is special about the project?
This project builds on the natural properties of bacteria to live in tumors and to use a gun-like mechanism for cell modification. In both respects, these traits are technically modified/enforced in order to be applied for cancer treatment. These natural properties have been shaped by evolution to function properly and are now slightly modified towards a therapeutic benefit. This interdisciplinary project thus combines expertise in microbiology, cell and tumor biology. Classical microbiology is combined with recently identified and highly promising cancer treatment approaches, in order to be able to employ well-known bacteria for state-of-the-art cancer therapy. Furthermore, the tight connection to T3 Pharmaceuticals ensures a transfer of resulting drug candidates for further development.
As the tumor colonization of our engineered bacteria relies on hallmarks of many solid tumors, it is independent of the identification of specific and detailed knowledge of tumor sub-types. It can thus be applied to solid tumors with high unmet medical need. The wide range of therapeutic proteins that can be delivered with our technology provides multiple opportunities for attack on cancer cells. We are convinced that this technology has the potential to be applied to the benefit of patients, which is our key motivation to develop this microbial therapy.
Within the frame of the project, the bacteria have been optimized for enzymatic conversion of a non-toxic substance into a highly toxic substance. In initial testing in murine models of cancer, the bacteria have demonstrated their therapeutic potential which will need to be confirmed in further experiments.
On a second track, the mode-of-action of the bacteria has been extended to the field of immuno-oncology. The principle of immune-oncology is to teach the patient’s immune system to fight the tumor. We have engineered several bacterial strains that have the potential to induce such an immune response at the tumor site. We have successfully confirmed the therapeutic potential of several of these strains in murine cancer models. The most promising candidate has been selected for further development towards clinical trials in cancer patients. The completion of the pre-clinical development is expected in 2019 which will allow to seek permission with health authorities to initiate clinical trials in 2020.
Ittig, S., Schmutz, C., Kasper, C.A., Amstutz, M., Schmidt, A., Sauteur, L., Vigano, M.A., Low, S.H., Affolter, M., Cornelis, G.R., Nigg, E.A., and Arrieumerlou, C., A bacterial type III secretion-based protein delivery tool for broad applications in cell biology. The Journal of cell biology, 2015. 211(4): p. 913-31.
Netzwerk Südbaden, Februar 2019, «Gründerzeit 2.0»
, print onlyInternational Feedback on Falling Walls Venture: The Telegraph IndiaFalling Walls Science Startup of the Year 2018
, Winner Falling Walls Venture, 8.11.18,Das beste Start-Up des Jahres kommt aus Basel
, Basler Zeitung, 9.11.18,Im Eisschrank war noch Platz
, Transkript, 11-12/18Bakterien züchten, um den Krebs zu bekämpfen – Startup der Uni Basel will Therapien entwickelnGegen Krebs: Bakterien statt Chemotherapie
, Nau.ch, 19.2.18BaseLaunch startet Phase II
, BaselArea.swiss, 30.1.18Startup.ch, TOP 100, die besten Schweizer Jungunternehmen
, Handelszeitung, 1.9.2017Ich erlebe in Basel ein sehr innovationsfreundliches Klima
, BaselArea.swiss, Interview mit Simon Ittig, 12.4.2017
Persons involved in the project
Dr. Simon Ittig
, project leaderDr. Marlise Amstutz
, research scientist, Biozentrum, University of Basel Dr. Falk Saupe
, research scientist, Biozentrum, University of Basel Dr. Christoph Schmutz
, Research Scientist, Biozentrum, University of Basel,Dr. Christoph Kasper
, project partner at T3 PharmaceuticalsProf. Dr. Erich Nigg
, project partner, Biozentrum, University of Basel Prof. Dr. Gerhard Christofori
, project partner, Department Biomedicine, University of Basel
Last update to this project presentation 02.12.2020