INTeRCePT: Intercept clonal evolution to overcome treatment resistance in childhood and adult blood cancer

Selected research findings

An ex vivo testing program was developed that allows tumor samples to be studied over time at the single-cell level under the influence of drug treatments. This enables the dynamic observation of both intracellular and extracellular processes as well as their responses to drug therapy. As a result, the role of clonal drivers of tumor growth and the interactions between tumor and immune cells can be better understood.

By analyzing the DNA of individual lymphoma cells, the clonal structure of the tumor cells could be precisely described. These insights help improve the understanding of genetic data and the effects of medications on these cell clones. Based on these findings, and in combination with other so-called multi-omics analyses, drug treatments were individually tailored. Currently, further studies and analyses are underway to continue optimizing these approaches.

The results of the research conducted so far form the basis for the development of the INTeRCePT Assay, a predictive testing method of low complexity, which is to be used in clinical studies. Initial results will be published shortly, while in parallel, ongoing data analyses are being conducted to integrate multi-omics data. The next step is to verify these results in clinical trials.

Clinical studies

In this context, a dataset was compiled containing over 300 samples from 40 lymphoma patients who had received various treatments — including CD19 CAR T-cell therapy. Because samples were collected at multiple time points both before and after the CAR T-cell treatment, a unique dataset was created that allows for the dynamic tracking of changes in immune responses and the tumor microenvironment.

Using advanced biomedical informatics analyses, new therapeutic strategies are now being developed to improve the effectiveness of CAR T-cell therapy. These analyses are expected to be completed within the next year.

Due to recent adjustments in the standard therapy for B-cell non-Hodgkin lymphomas, the study design was revised in consultation with the scientific advisory board. The focus is now on the validation of the INTeRCePT Assay. This represents an important breakthrough that will form the basis for future studies and optimized treatment strategies, laying the groundwork for more targeted interventional studies.

Outlook

In the next twelve months, ongoing experiments and analyses are scheduled to be completed. A key focus will be to gain a deeper understanding of the immune landscape in non-Hodgkin lymphomas. Using multi-omics analyses, the project aims to identify prognostic biomarkers and target molecules for new therapeutic interventions. The INTeRCePT Assay will help increase the efficiency of these analyses and enable better classification of patient groups in future studies, thereby facilitating more targeted therapies.

In parallel, standardized structures for clinical trials and a secure data system are being developed for the Innovation Clinic. Data from more than 300 registered patients – including treatment histories and biobank data – will be documented and made available for research purposes. This will further drive the development of personalized therapies.

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