An Organotypic Tumor Microenvironment (oTME) Model for High-throughput Discovery of Anti-cancer Therapeutics

Technology Summary

This technology provides a method to replicate the tumor microenvironment (TME) ex vivo for high-throughput discovery of anti-cancer therapeutics and therapeutic targets.

Technology Overview

The development and growth of solid tumors relies on their surrounding tumor microenvironment (TME), which consists of several types of non-malignant cells. One of these cell types, named tumor-associated macrophages (TAMs), are of great interest to biomedical studies because they are critical to enhance proliferation, angiogenesis, and immune evasion of tumor cells. While the immunosuppressive TAMs are considered a highly promising therapeutic target for various solid tumors, researchers must rely on systems that are either non-scalable (e.g., mouse models) or incapable of accurately recapitulating the TME in patients (e.g., in vitro cell culture) when screening for drugs and drug targets. As such, there is a need for research tools that accurately model the TME to accelerate the discovery of therapeutics targeting the pro-tumorigenic functions of TAMs.

This technology provides an organotypic TME (oTME) model with remarkable scalability and a high resemblance to the TME in patients. The oTME is an ex vivo system derived from murine mammary tumors by integrating the tumor cells with the TME components (e.g., stromal cells, immune cells including T cells, NK cells and macrophages) from the same tumor, allowing for the maintenance of the intercellular interactions between tumor cells and other cells. Therefore, the oTME can recapitulate the human TME in vivo with high fidelity. Moreover, unlike conventional in vitro cell cultures, the oTME is exceptionally stable in culture (>2 month), scalable, self-sustained, with minimal requirement for the addition of growth factors or basement membrane proteins, which makes it suitable for high-throughput screening of TME immune-targeting therapeutics. In a proof-of-concept study, the inventors successfully identified novel anti-cancer drug targets and drug candidates that can revert TAMs to immuno-reactive state, block TAM proliferation and significantly inhibit tumor growth.

Potential Applications

• High-throughput anti-cancer drug target discovery
• High-throughput anti-cancer drug discovery
• Mechanistic research on tumorigenesis, metastasis, and immune evasion in TME

Advantages

• High resemblance to the human tumor microenvironment (TME)
• Scalability enables high-throughput screens
• Exceptional stability (>2 months) in culture
• Self-sustained (No requirement of growth factors or basement membrane proteins)