GLICO Platform: Patient-Specific Brain Tumor Organoids for Precision Drug Development

Background & Unmet Need

• Glioblastoma (GBM) remains an incurable cancer with a poor prognosis (median survival ~15 months)
• Despite many efforts, there has been little progress in developing effective treatments for GBM, and its biology remains incompletely understood
• One barrier to developing new therapies is that current preclinical models of GBM do not reflect the biology or genetics of primary tumors
• Modeling GBM’s interaction with the tumor microenvironment has also been a challenge and has yet to be successfully replicated
• Unmet Need: Preclinical models of GBM which reflect the biology, genetics, and environment of in-situ tumors and can be used for the development of effective therapies

Technology Overview

• The Technology:A patient-specific platform for modeling GBM and its TME in an organoid culture
• Tumor-bearing organoids are generated by co-culturing patient-derived glioma stem cells (GSCs) with hESC-derived cerebral organoids
• The resulting organoids have tumors grown from from patient-derived GSCs embedded within them
• PoC Data: GLICO models demonstrate tumor proliferation and infiltration, with 20% of tumor cells staining positive for Ki67
• GLICO organoids display similar pathology to GBM patients, like spontaneous microtubule formation
• Response rates to GBM drugs in GLICOs are closer to in vivo rates compared to 2D cultures (24-43% GLICO vs 80-90% cell line), and vary by patient
• RNA-seq data shows that GLICO transcriptomes are significantly more correlated to those of patient tumors than current GBM models

Technology Applications

• High-throughput screening for glioblastoma drug development and neurotoxicity studies
• Patient-specific screening for personalized medicine
• Identification of new therapeutic targets for GBM
• Understanding of basic GBM biology and interaction with tumor-microenvironment

Technology Advantages

• GLICOs can be maintained in culture for 4 months or longer
• GLICO models reflect the basic biology of GBM better than 2D cultures and traditional organoids
• Organoids and their environments are easy to manipulate and control for experimentation
• GLICO models are easily scalable, making them an ideal candidate for high-throughput screening

Figure 1: GLICO models recapitulate patient-derived cell line behavior via differentiated patterns of invasion. More aggressive cell lines (0728, 1206) demonstrate more diffuse patterns of invasion compared to slower-growing cell lines (0517, 0607). GSCs are labeled with GFP.