Study

Functional screening on patient-derived organoids identifies a therapeutic bispecific antibody that triggers EGFR degradation in LGR5+ tumor cells

Study ID Alternative Stable ID Type
EGAS00001004584 Other

Study Description

Patient-derived organoids (PDOs) have demonstrated predictive value in prospective clinical trials supporting selection of personalized treatments. Because PDOs retain the organization and physiological functions of their source tissue, PDO biobanks could also be an ideal substrate to screen for novel therapeutic interventions. Here we describe a large-scale functional screen of dual targeting bispecific antibodies (bAbs) on a colorectal cancer (CRC) PDO biobank to target their dependency on cancer stem cells. A novel drug discovery pipeline was assembled where therapeutic bAb panels generated against WNT and receptor tyrosine kinases (RTK) targets were functionally evaluated by high content imaging to capture the complexity of PDO responses across a wide range of different CRCs and paired normal colonic mucosa samples. Our strategy resulted in a bAb that specifically triggers EGFR degradation in LGR5+ CSCs and that exhibits unique therapeutic properties such as potent growth inhibition of KRAS mutant CRCs, blockade of metastasis initiation in preclinical models and minimal ... (Show More)

Study Datasets 1 dataset.

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Dataset ID Description Technology Samples
EGAD00001008445
Functional screening on patient-derived organoids identifies a therapeutic bispecific antibody that triggers EGFR degradation in LGR5+ tumor cells
Illumina HiSeq 2000 131

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