MORAG PARK

Development of a high throughput bioprinted 3D human tumor microenvironment assay that recreates immune “hot” and “cold” tumors

Challenge: Solid tumor growth is regulated by complex interactions of tumor cells with an assortment of adjacent non-malignant cells collectively referred to as the tumor microenvironment (TME). In “triple-negative breast cancer” (TNBC), which represents 15 to 20 % of all breast cancers, tumors can be characterized as “immune hot” or “immune cold” with respect to the level of infiltration of immune cells within it. In general, a lack of T cell immune infiltration within the tumor epithelial areas correlates with poor prognosis. As only a minority of cancer patients respond to current chemotherapies as well as immunotherapies, new modulators to the TME are needed to overcome these mechanisms and improve patient outcome. A major barrier to the efficient development of cancer therapeutics is the availability of in vitro experimental models that accurately reflect the in vivo immune and tumor microenvironment along with its spatial complexity.

Solution: The goal of the project is to establish and validate an in vitro 3D tumor model that more accurately reflects different immune subtypes of the TNBC in vivo tumor microenvironment and the spatial relationship between TME components. Furthermore, the 3D-TNBC model will be adapted for high-throughput assay suitable for larger-scale screening programs. To achieve these objectives, biobanking of TNBC patient-derived tumor components and gene expression analysis is performed to identify genetic differences between immune “hot” and “cold” tumors and bioprinting is designed to recapitulate TME in spatially distinct ways. Pharmacological responses will then be tested using drugs with known clinical effects.

Expected Achievements/Impact: The team will develop a TNBC tumor bank of human tissue-matched TME cell components consisting of three distinct enriched cell populations (tumor epithelial cells, fibroblasts, and immune cells). At the end of the project, the team will deliver protocols for 3D bioprinting of tumors as well as validated 96-well format 3D bioprinted tumor model that mimics immune “hot” and “cold” tumors suitable for small molecule or immuno-therapy screening. This technology will facilitate the development of new targeted therapies capable of eradicating highly aggressive breast cancers for which there are currently few treatment options available to the young women most affected by them. The 3D assay will also have broad applicability across many solid tumor types and treatment modalities by providing personalized medicine approaches using patient-specific tumor components as well as throughout the drug development pipeline by improving its efficiency.

 

 

 

 

 

 

 

 

 

 

 

 

Principal Investigator:


Morag Park
McGill University

Co-investigators

Christopher Moraes
Connie Krawczyk

McGill University

Samuel Wadsworth
Aspect Biosystems

Ongoing Project
$ 2,120,254 / 2 years
Supported by CQDM through:
• Merck
• GSK
• MEI
 
And by co-funding partners:

• Canadian Cancer Society (CCS)
• Aspect Biosystems
• McGill University