IM JAHR 2016 BEWILLIGTES PROJEKT

Microbial Treatment of Solid Tumors – Microbials 2016

Redaktion

Für den Inhalt der Angaben zeichnet die Projektleitung verantwortlich.


Kooperation

This project is one of the five winners of the call 2016 «Microbials – Direct Use of Micro-Organisms».

Project partners: Biozentrum der Universität Basel; Department of Biomedicine, University of Basel; Krebsliga beider Basel; T3 Pharmaceuticals AG


Projektdaten

Projekt-Nr.: GRS-059/16
Förderbeitrag: CHF 400'000
Bewilligung: 02.11.2016
Dauer: 01.2017 - 12.2018
Handlungsfeld: Microbials, seit 2016


Microbial Treatment of Solid Tumors – Microbials 2016
Projekt nummerGRS-059/16 BudgetCHF 400'000 VerantwortlichSimon Ittig Laufzeit01.2017 - 12.2018

Effector delivery by Contractile Injection Machines – Microbials 2016
Projekt nummerGRS-058/16 BudgetCHF 352'000 VerantwortlichMartin Pilhofer Laufzeit01.2017 - 12.2019

A Specific Mechanosensitive Bacterial Tumor Therapy – Microbials 2016
Projekt nummerGRS-057/16 BudgetCHF 374'000 VerantwortlichAlexandre Persat Laufzeit05.2017 - 04.2020

Microorganism-based Biosensor – Microbials 2016
Projekt nummerGRS-056/16 BudgetCHF 450'000 VerantwortlichJan Wendelin Stark Laufzeit01.2017 - 12.2019

Therapeutic Fungi – Microbials 2016
Projekt nummerGRS-055/16 BudgetCHF 480'000 VerantwortlichBenjamin Marsland Laufzeit01.2017 - 01.2020


Projektleitung

Dr. Simon Ittig, University of Basel, Biozentrum, Klingelbergstrasse 50/70, 4056 Basel (Schweiz), simon.notexisting@nodomain.comittig@unibas.notexisting@nodomain.comch


Abstract

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.

Was ist das Besondere an diesem Projekt?

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.

Stand/Resultate

We are currently using in vivo cancer models to validate the therapeutic potential of our first drug candidate. With the here-described project we will now extend the mode of action of bacterial attack on tumor cells. Firstly, bacteria will be engineered for immuno-oncology by induction of specific immune responses at the tumor site. Secondly, the bacteria are optimized for enzymatic conversion of a non-toxic substance into a highly toxic substance. In following steps, these newly generated bacterial strains will be assessed for their potency in tumor treatment using murine models of cancer.

Publikationen

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.

Medienecho

«Bakterien sollen Krebs bekämpfen», BAZ print journal, 2.7.2016;
Venture.ch business plan competition, winner 2016; access via: venture.ch; 1.7.2016

Links

Biozentrum – Technology Ventures
T3 Pharmaceuticals

Am Projekt beteiligte Personen

Dr. Marlise Amstutz, research scientist, Biozentrum, University of Basel
Dr. Falk Saupe, research scientist, Biozentrum, University of Basel
Dr. Christoph Kasper, project partner at T3 Pharmaceuticals
Prof. Dr. Erich Nigg, project partner, Biozentrum, University of Basel
Prof. Dr. Gerhard Christofori, project partner, Department Biomedicine, University of Basel

Letzte Aktualisierung dieser Projektdarstellung

03.04.2017