ARTificial Tumour Immune MicroEnvironment for structured profiling of cancer immune adaptation
Lead Research Organisation:
University of Oxford
Department Name: Kennedy Institute
Abstract
Within the framework of ART-TIME, I will develop an artificial tumour immune microenvironment (ART-TIME) for human pancreatic cancer organoids empowering structured and rational analysis of tumour immune adaptations. Immune cells, the defining elements of an immune microenvironment, will thus be recreated as synthetic cells by bottom-up assembly from their single molecular building blocks. The programmable synthetic cells will be introduced into tumour organoids to function as lifelike leukocyte mimics presenting immune effector functions. By this, a molecularly defined immune environment will be created inside tumour models for the first time. Imaging-based multi-parametric screenings will assess organoid development as well as immunotherapy response as a function of the ART-TIME configuration. This strategy will link TIME architectures to cancer immune adaptation and evasion for quantitative description of therapy resistance. Therefore, ART-TIME strives to de-convolute the dynamic complexity of the tumour immune microenvironment towards a rational dissection. Moreover, ART-TIME will contribute concepts for the assembly of hybrid biomaterials that embody essential features of living cells. Within this fellowship, hosted at the University of Oxford by Prof. Michael Dustin, I will contribute fundamental knowledge on tumour immunology using programmable man-made materials. My geographic transition into a research environment with clinically oriented infrastructure will significantly expand my scientific horizon and refine my academic profile. Greatly profiting from the synergy between my expertise on bottom-up synthetic biology and the host's highquality research on immunology, this interdisciplinary project will open up broad perspectives for synthetic cells capable of manipulating tissue patterns by creating hybrid materials at the vanishing boarders between the living and non-living world - the envisioned focus of my subsequent research career.
Publications
Burgstaller A
(2024)
Soft Synthetic Cells with Mobile Membrane Ligands for Ex Vivo Expansion of Therapy-Relevant T Cell Phenotypes.
in Small (Weinheim an der Bergstrasse, Germany)
Cortacero K
(2023)
Evolutionary design of explainable algorithms for biomedical image segmentation.
in Nature communications
| Description | Oskar Staufer was supported by the UKRI funded Marie Curie fellowship for about 3 months as after the acceptance process he received an offer to start his own lab at the University of Saarland with pressure to start immediately due to teaching. So we terminated the grant after 3 months. In this time Oskar contributed to the collaboration with the Valitutti group in Toulouse on the Cartesian Genetic Programming algorthithm and contributed to demonstration it could be used to track natural ~100 nm particles such as extracellular vesicles and supramolecular attack particles that are components of the tumour microenvironment and thus relevant to the aims of this EPSRC funded project. This work was published in 2023. Oskar's lab in USAAR is thriving. It is developing the themes of the application related to artificial cells and tumour microenvironment in this lab at USAAR. |
| Exploitation Route | The software developed by the Toulouse group will be validated for use in tracking small biological particles and this will be of wide utility. The software is also useful for analysis of tumour microenvironment. There will likely be at least one more paper citing the EPSRC support related to work with giant unilamellar vesicles are surrogate cells in studies with T cell engagers, biologics that are use to help the immune system kill chancer cells. |
| Sectors | Manufacturing including Industrial Biotechology Pharmaceuticals and Medical Biotechnology |
| Description | Bottom-up synthetic immunology is gaining significant traction: https://www.nature.com/articles/s41565-024-01744-9 https://advanced.onlinelibrary.wiley.com/doi/full/10.1002/anbr.202400037 Following our presentations in Heidelberg (where we met last year), Heidelberg University launched a Spotlight Project on Synthetic Immunology: https://www.uni-heidelberg.de/en/research/research-profile/excellence-strategy/engineering-molecular-systems/spotlight-project-synthetic-immunology OS efforts funded by UKRI are contributing to establishing a new field. |
| Sector | Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Policy & public services |
| Description | Royal Society Innovation and Entrepreneurship events |
| Geographic Reach | National |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Description | Synthetic cell-based analysis of biophysical adaptations in the tumor immune microenvironment |
| Amount | € 2,400,000 (EUR) |
| Funding ID | 525255627 |
| Organisation | German Research Foundation |
| Sector | Charity/Non Profit |
| Country | Germany |
| Start | 01/2023 |
| End | 01/2028 |
| Title | Cartesian Genetic Programming algorithm for quantification of extracellular vesicles and supramolecular attack particles |
| Description | The Valitutti lab and collaborators in Computer Science in Toulouse developed the algorithm. Oskar Staufer provided materials to demonstrated that the Cartesian Genetic Programming could be trained to identify the particles and also to learn how it did this. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2023 |
| Provided To Others? | Yes |
| Impact | The algorithm has been patented and the first author of the paper from Toulouse has spun out a company to develop it. |
| Description | ATTACK consortium |
| Organisation | Saarland University |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | We have joined in a consortium to further study and develop supramolecular attack particles, which was one of the subject of the CRUK planning funds. We have provided preliminary data, writing and editing. Update as of 2/3/21- The synergy grant received a fundable score for a total award of ~€10M. We are working on completing the grant agreement. https://erc.europa.eu/sites/default/files/document/file/erc-2020-syg-results.pdf |
| Collaborator Contribution | Jens Rettig is the PI of the grant. Cosima Baldari (a partner in the CRUK accelerator application) and Salvatore Valitutti are co-investigators. |
| Impact | We have written an ERC Synergy Grant together that is at second stage of review. We have a paper submitted with the group from Toulouse. Our synergy grant was selected for funding and we are working towards a start date of 1 May 2021. |
| Start Year | 2019 |
| Description | ATTACK consortium |
| Organisation | University of Siena |
| Country | Italy |
| Sector | Academic/University |
| PI Contribution | We have joined in a consortium to further study and develop supramolecular attack particles, which was one of the subject of the CRUK planning funds. We have provided preliminary data, writing and editing. Update as of 2/3/21- The synergy grant received a fundable score for a total award of ~€10M. We are working on completing the grant agreement. https://erc.europa.eu/sites/default/files/document/file/erc-2020-syg-results.pdf |
| Collaborator Contribution | Jens Rettig is the PI of the grant. Cosima Baldari (a partner in the CRUK accelerator application) and Salvatore Valitutti are co-investigators. |
| Impact | We have written an ERC Synergy Grant together that is at second stage of review. We have a paper submitted with the group from Toulouse. Our synergy grant was selected for funding and we are working towards a start date of 1 May 2021. |
| Start Year | 2019 |
| Description | ATTACK consortium |
| Organisation | University of Toulouse |
| Country | France |
| Sector | Academic/University |
| PI Contribution | We have joined in a consortium to further study and develop supramolecular attack particles, which was one of the subject of the CRUK planning funds. We have provided preliminary data, writing and editing. Update as of 2/3/21- The synergy grant received a fundable score for a total award of ~€10M. We are working on completing the grant agreement. https://erc.europa.eu/sites/default/files/document/file/erc-2020-syg-results.pdf |
| Collaborator Contribution | Jens Rettig is the PI of the grant. Cosima Baldari (a partner in the CRUK accelerator application) and Salvatore Valitutti are co-investigators. |
| Impact | We have written an ERC Synergy Grant together that is at second stage of review. We have a paper submitted with the group from Toulouse. Our synergy grant was selected for funding and we are working towards a start date of 1 May 2021. |
| Start Year | 2019 |
| Description | Collaboration agreement with Boehringer Ingelheim |
| Organisation | Boehringer Ingelheim |
| Country | Germany |
| Sector | Private |
| PI Contribution | This position supported a PDRA for 2 years. These was extended to 2.5 years due to recruiting and a no cost extension. The collaboration was important in that it provided access to bispecific engagers for use in immunological synapse analysis. We would like to better understand this class of drug candidates for future development of therapeutics. I supervised the PDRA working on the project and we have written a paper that has been posted on biorxiv. |
| Collaborator Contribution | They provides FEC funding for the project plus ~ 20,000 in reagents. We had periodic meetings with the senior scientists and have recently engaged in a collaboration with a PDRA based within the company in Germany. |
| Impact | Staufer O, Leithner A, Zhou S, Crames M, Comeau S, Young D, Low S, Jenkins E, Davis SJ, Nixon A, Pefaur N, Kasturirangan S, Dustin ML. Segmental flexibility of bispecific T-cell engagers regulates the dynamics of immune synapse formation. bioRxiv. 2022:2022.06.15.496334. doi: 10.1101/2022.06.15.496334. |
| Start Year | 2021 |
| Description | Woods Hole Marine Biology Lab Physiology Course |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | OS, PC, EJ and MLD participated in prestigious Woods Hole Physiology course, which attracts students from around the world inluding North America, South America, Europe, Asia, Africa and Australia. There were daily lectures, one delivered by MLD, and other events. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.mbl.edu/education/advanced-research-training-courses/course-offerings/physiology-modern-... |