© M.Boutros DKFZ 2018 Automated microscopy: test substance changes cellsDKFZ: Machine Learning to Accelerate Drug Research

October 2018: The European Research Council (ERC) awarded a "proof-of-concept grant" to Michael Boutros from the Deutsches Krebsforschungszentrum Heidelberg (DKFZ). His project "REMATCH - Image-based Analysis for Drug Discovery and Repurposing" enables the development of new as well as established drugs more cheaply and quickly using image-based analyses.

The idea for REMATCH came from Dr Boutros' earlier ERC project "SYNGENE". It is based on software for© Michael C Boutros 2017 automated image-based screenings of a large number of reactions of cells to active substances using machine learning methods. Each test substance causes subtle changes in the structure and distribution of these biomolecules, which are made visible by fluorescence staining and documented by automated microscopy. However, in order to be able to interpret the biological meaning of such an image, a reference must be available to the users of the method. With REMATCH, the researchers around Boutros now want to create a reference database for such drug patterns. They are using new approaches in artificial intelligence and machine learning.

The very large data sets of the reference database are used to compare the effect of a test substance with that of already approved or failed active substances (so-called "fallen angels") in order to exclude side effects at an early stage and to explore new fields of action. The ERC funding now enables Boutros to test the economic potential as well as the possibility of a spin-off of the project. Source: DKFZ

 B2Bioworld Editor's Note

IOmx AG: Cancer Bio-Drug Discovery Platform for the “Immune Modulatome”  

Oktober 2018. Frequently patients are unresponsive to immunotherapies, for example with the many monoclonal antibodies currently on the market. Those under development expectably run into the same problems. One of the reasons is that tumour cells remodel immune checkpoints either to prevent recognition, or to downregulate an immune response, for instance by releasing immunosuppressive cytokines. How can immune tolerance in tumour cells be overcome? One promising approach is to map what Woo et al. (2012) termed the “immune modulatome”, that part of all immune-inhibitory pathways in an organism which allows tumour cells to escape. Discovering so-called immune regulatory circuits is an approach to determine early on how to overcome resistance of tumour cells to molecules for immune therapy.

For some years Boutros, Beckhove, Khandelwal and colleagues (2015) have been developing methods and business models for cancer drug discovery, some of them together with Bayer Healthcare (Andreas Busch) at DKFZ. At issue is to provide to pharma R&D a broader picture of biological functions of therapeutic molecules beyond one or two immune checkpoints.

With his work on cell signalling Dr Boutros’ has been developing an automated platform to screen resistance of tumour cells to cytotoxic T-lymphocytes which can also applied to test molecules and compounds either already on the market or drug candidates. The REMATCH project “Image-based analysis for drug discovery and repurposing» started beginning August and runs for 18 months. It is funded with 149,500 Euros at DKFZ. This money is provided «(i) to develop a cloud-based infrastructure for analyses of image-based drug screening (WP1), (ii) to perform a proof-of-concept screen to create a reference database and a showcase for commercialization (WP2), (iii) to conduct market analyses and development of a business plan for a spin-off company.» Major parts of «the proof-of-concept» have already been provided to be incorporated into an ongoing start-up which integrates drug screening up to testing immunotherapeutic molecules in clinical trials.
In April 2016 Nisit Khandelwal, former Liaison Researcher of DKFZ with Bayer Healthcare in their Joint Immunotherapy Laboratory, founded Immodutome AG (today IOmx AG) with biotech investors Sebastian Meier-Ewert and Elmar Maier as contract research in immunotherapy drug discovery. Seven months later they filed a first patent which was granted last May. With Michael Boutros Philip Beckhove is another key inventor from DKFZ. Until recently Dr Beckhove was Head of Translational Immunology at DKFZ where he also managed the collaboration with Bayer. Since 2015 he is heading Interventional Immunology at the University Hospital at Regensburg, a unit dedidated to clinical trials of drugs for immunotherapy. Mid-december 2017 IOmx hired Apollon Papdimitriou who left Roche Penzberg, where he had global responsibility for Bioanalytical R&D of Large Molecules. While MPM Capital (Sebastian Meier-Ewert) is the lead investor, Merck Ventures acquired a strategic stake since the company’s beginning. Clearly, IOmx is set to accommodate Dr Boutros’ development for screening and repurposing small and large molecules for cancer therapies. wk

References

Khandelwal N, Breinig M, Speck T, Michels T, Kreutzer C, Sorrentino A, Sharma AK, Umansky L, Conrad H, Poschke I, Offringa R, König R, Bernhard H, Machlenkin A, Boutros M, Beckhove P (2015): A high-throughput RNAi screen for detection of immune-checkpoint molecules that mediate tumor resistance to cytotoxic T lymphocytes- EMBO. February 17: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4403046/.

Woo SR, Turnis ME, Goldberg MV, Bankoti J, Selby M, Nirschl CJ, Bettini ML, Gravano DM, Vogel P, Liu CL et al (2012): Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Research 72: 917 – 927.

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