Generation and validation of a panel of EMT reporter cell lines from solid tumors

Project Information

seEMT

Grant agreement ID: 101069235

DOI

10.3030/101069235

Project closed

EC signature date 2 June 2022

Start date 1 July 2022

End date 31 December 2023

Funded under

• European Research Council (ERC)

Total cost

No data

EU contribution

€ 150 000,00

Coordinated by

MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT (MDC)
Germany

Periodic Reporting for period 1 - seEMT (Generation and validation of a panel of EMT reporter cell lines from solid tumors)

Reporting period: 2022-07-01 to 2023-12-31

Summary of the context and overall objectives of the project

The ERC Proof of Concept Grant seEMT aimed to address the high failure rate in anticancer drug discovery and development, which may be partially attributed to the use of oversimplified and inaccurate cell line models for studying human tumors. Specifically, we worked towards the generation and validation of a panel of EMT (Epithelial-to-Mesenchymal Transition) reporter cell lines from solid tumors.
The Problem: Current models for anticancer in vitro drug discovery do not accurately reflect the complexity of the diseases in vivo.
The Solution: The project aimed to incorporate into the drug discovery pipeline, cellular mechanisms like the epithelial vs. mesenchymal states, which have roles in solid tumor progression and their impact on therapeutic responses. We proposed to create a toolkit of ready-to-use cell lines and defined cell culture media that can represent any kind of solid tumor subtype. This approach is novel in that it incorporates complex cellular states into in vitro and ex vivo drug-discovery research. It uses custom synthetic genetic reporters in tumor models to trace both epithelial and mesenchymal tumor cell states, which can potentially reduce the high failure rate in early anticancer drug discovery.
Innovative Approach: seEMT revolves around an innovative method involving the computer-assisted identification of cell-type-specific cis-regulatory elements and the automated generation of a synthetic cis-element reflecting such cell identity or state. This approach aims to bring drug discovery research to a new level by improving the clinical predictive power of solid tumor models.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Executive Summary

Our team has achieved significant milestones in the development and optimization of cell lines for cancer research, with a focus on enhancing the study of solid tumors. Key achievements and future strategies for commercial exploitation include, but are not limited to:

1. Establishment of Cell Lines with Validated Reporters

We have successfully established several cell lines equipped with validated reporters. This achievement marks a pivotal step in our research, as these cell lines are crucial for studying cancer behavior and response to treatments. Furthermore, we have implemented a procedure to make these cell lines available to both academic and commercial partners, fostering collaboration and advancement in the field.

2. & 3. Optimization of Propagation Conditions

Our team has established optimal conditions for propagating the cell lines we selected in both (neuro)epithelial and mesenchymal states. This was achieved through the careful selection of appropriate media and supplements, ensuring the robust growth and maintenance of these cell lines. This optimization is vital for accurately studying cancer cells in different states and contributes significantly to the reliability of our research, thereby being a critical resource for others with similar ambitions.

4. Proof of Concept for Treatment Response

We have obtained Proof of Concept (PoC) that the optimized conditions directly affect the response of individual cell lines to anti-cancer treatments. This finding is crucial as it highlights the potential of toolkit to model treatment responses accurately, thereby aiding in the in vitro development of cancer therapies that have increased predictive potential for subsequent (pre)clinical testing.

5. Definition of Optimal Readouts

In line with industry standards, we have defined the optimal readouts for our experiments. This ensures that our research outcomes are not only reliable but also relevant to current industry practices, enhancing the applicability of our work in real-world scenarios.

6. Commercial Exploitation Strategies

Our team has developed comprehensive strategies to move forward with the commercial exploitation of our advancements. This includes plans to collaborate with selected partners, leveraging our research to contribute to the broader field of cancer therapy development.

7. Improving Accuracy and Efficiency in Solid Tumor Studies

The successful examples gathered from points 1 to 5 have demonstrated our potential to significantly improve the accuracy and efficiency in studying solid tumors. The achievements in developing these cell lines and optimizing their conditions pave the way for more precise and effective research in this area.

Future Outlook

Our ongoing efforts include a solid plan to explore commercialization opportunities with interested partners. This plan is guided by our achievements and the promising potential they hold for the advancement of cancer research and therapeutic development. This will be amplified by planned publications and dissemination of the results described above, followed by execution of the commercial planning drafted herein.

Conclusion

The progress we have made in the development and optimization of cell lines, along with our strategy for commercial exploitation, positions us at the forefront of innovation in cancer research. We are committed to continuing our work in this field, towards contributing to the global effort to translate academic research into effective anti-cancer therapeutics to the benefit of all the relevant stakeholders.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Incorporating cellular phenotypes that surpass tumor genotypes in influencing treatment response represents a leap beyond current drug discovery standards, showcasing innovation that features the definition of beyond state-of-the-art.