Ex vivo drug testing in metastatic biopsies reveals patient-specific vulnerabilities to cancer targeting and immune activating drugs

Abstract

Biomarker-guided therapies in oncology often fail to induce considerable responses in patients with advanced cancer. As a complementary approach, direct drug testing on individual patient samples is highly attractive yet is currently hampered by the lack of assays that combine (i) fast reporting, (ii) the ability to inform about immune-mediated responses, (iii) robust quantification, and (iv) scalability for parallel assessment of multiple drugs. Here, we introduce our patient-derived ex vivo drug response assay (PEDRA) that fulfills all these requirements. Using malignant pleural effusions (MPEs) from five non-small cell lung cancer (NSCLC) patients with detailed clinical treatment histories, we tested 52 guideline-recommended therapies and eight investigational antibody-drug conjugates (ADCs). In all patients, PEDRA identified treatment options that outperformed the therapies the patients had received. The results reflected clinical observations as well as expectations derived from mutational profiling and disease courses. To extend the applicability of PEDRA beyond MPEs to other metastatic lesions, we generated a protocol starting from core needle biopsies. Owing to its reproducible and quantitative nature, PEDRA may provide a valuable diagnostic tool to guide time-sensitive clinical therapy decisions. Additionally, PEDRA has great potential for preclinical testing of investigational drugs, thereby reducing the need for animal experiments.