Expert Spotlight
Lorenz Rognoni, PhD
How does the tumor microenvironment change after treatment with a new drug candidate?
Relevant for
Biopharma, CROs
Overview. After the identification and initial work to determine a potential new drug candidate, data from a small Phase 1 study with a low number of patients and multiple drug doses is available. Tumor samples were collected pre-treatment and post-treatment and from earlier studies the drug candidate’s expected mode of action is known. Using a pre-defined panel, this study is aimed at determining how the cells in the tumor microenvironment responded to treatment during the trial.
Study Plan
Confirm the mode of action for a potential treatment and identify that a set of biomarkers behave as predicted
Samples available: Confirm the mode of action for a potential treatment and identify that a set of biomarkers behave as predicted.
Staining and imaging: Based on earlier work to determine the biomarkers, an 8-plex staining panel is chosen to investigate the tumor microenviroment on all samples, followed by same-slide H&E staining.
Image analysis: To detect the phenotypes of interest and evaluate the immune response, standard image analysis was applied to all samples with the addition of pathologist review of the results. With the small number of samples and limited tissues available, extra care was taken to maximize the information that could be extracted from each sample. The results include:
- Tissue detection
- Coarse artefact exclusion (folds, blur, bubbles, red blood cells)
- Cell detection via nucleus identification (DAPI)
- Phenotyping based on marker positivity
- Densities and percentages of phenotypes based on the defined panel
- Region detection of epithelium and surrounding areas
- Pathologist review of results
Data Analysis: All image analysis data was collected and analysis per marker and phenotype was plotted for up or down regulation pre- and post-treatment.
Results delivery
Changes to the tumor microenvironment upon drug treatment are delivered in clear and effective graphs that enable discussion of the expected outcomes of the drug’s mode of action.
The results were presented in a comprehensive report showing line plots pre- and post-treatment, including any trend information or outliers that might be notable. These results were then discussed with the researchers as well as the in-house pathologist to evaluate whether the results are as expected for the mode of action of the drug candidate.
