Document resource
Background Unlike cytotoxic chemotherapies, immunotherapies require an intact tumor microenvironment (TME) unique to each patient, and there are no functional precision medicine assays that can accurately predict individual patient response to immunotherapy in a clinically actionable timeframe. The E-slice platform is a proprietary 3D human tumor tissue culture system that enables rapid, personalized drug sensitivity testing in 8-12 days. This platform preserves individual patient tumors’ histoarchitecture and cellular composition, including tumor-infiltrating immune cells, and the spatial relationships among different cell types, enabling the evaluation of immunotherapies ex-vivo.Methods E-slices are generated from fresh patient tumor tissues containing tumor-trained immune and other stromal cells. This contrasts with other 3D systems, where immune cells are artificially introduced after cancer cells have been selected and grown out in culture. E-slices are cultured in serum-free, chemically defined medium that does not have cytokines or growth factors that can artificially activate or suppress immune cells. Single-cell RNA-sequencing validation confirmed that E-slices maintain immune cells in their native states for up to 8 days ex vivo.In this prospective clinical study, 14-gauge biopsy cores from newly diagnosed triple-negative breast cancer (TNBC) patients intended to receive neoadjuvant immunochemotherapy per the KEYNOTE-522 regimen at MD Anderson Cancer Center were enrolled in the study. E-slices were generated from the first 14 patients and treated with IgG control, pembrolizumab, paclitaxel plus carboplatin, doxorubicin plus cyclophosphamide, or a combination of pembrolizumab with doxorubicin plus cyclophosphamide (days 1—4 ex vivo) and then switched to paclitaxel plus carboplatin (days 4-12, maintenance). E-slice responders were defined as samples with a statistically significant reduction in viability at day 12 compared to baseline. Patient tumor responders were defined only by pathological complete response (pCR) at the time of surgery, after standard-of-care neoadjuvant chemoimmunotherapy treatment.Results Except for one sample, which arrived at room temperature, E-slice assays were successfully set up with all patient biopsies, achieving the primary endpoint. Ex-vivo pembrolizumab response rate was 14% (2 of 14 samples evaluated thus far), which is remarkably similar to clinical response rates reported in the KEYNOTE-522 trial.Conclusions E-slice assay may predict TNBC patient responses to pembrolizumab by providing drug sensitivity data in a clinically actionable time frame.