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Microfluidic Co-Culture Models for Dissecting the Immune Response in in vitro Tumor Microenvironments
Published on: April 30, 2021
Engineering Biomaterials to Model Immune-Tumor Interactions In Vitro
Arianna Skirzynska1,2, Chang Xue2,3, Molly S Shoichet1,2,3,4
1Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON, M5S 3E5, Canada.
Abstract:
Engineered biomaterial scaffolds are becoming more prominent in research laboratories to study drug efficacy for oncological applications in vitro, but do they have a place in pharmaceutical drug screening pipelines? The low efficacy of cancer drugs in phase II/III clinical trials suggests that there are critical mechanisms not properly accounted for in the pre-clinical evaluation of drug candidates. Immune cells associated with the tumor may account for some of these failures given recent successes with cancer immunotherapies; however, there are few representative platforms to study immune cells in the context of cancer as traditional 2D culture is typically monocultures and humanized animal models have a weakened immune composition. Biomaterials that replicate tumor microenvironmental cues may provide a more relevant model with greater in vitro complexity. In this review, the authors explore the pertinent microenvironmental cues that drive tumor progression in the context of the immune system, discuss how these cues can be incorporated into hydrogel design to culture immune cells, and describe progress toward precision oncological drug screening with engineered tissues.
Insights
Engineered biomaterials offer advanced in vitro models for cancer drug screening by mimicking tumor microenvironments and incorporating immune cells, potentially improving preclinical evaluation and clinical success rates.
Area of Science:
- Biomaterials Science
- Cancer Biology
- Immunology
Background:
- Traditional 2D cell cultures lack the complexity of the tumor microenvironment.
- Existing preclinical models often fail to account for immune cell interactions crucial for cancer drug efficacy.
- Low success rates in cancer drug clinical trials highlight limitations in current preclinical evaluation methods.
Purpose of the Study:
- To review the role of engineered biomaterial scaffolds in cancer research.
- To discuss the incorporation of tumor microenvironmental cues into biomaterial design for immune cell culture.
- To explore the potential of engineered tissues for precision oncological drug screening.
Main Methods:
- Review of literature on biomaterial scaffolds, tumor microenvironment, and cancer immunotherapies.
- Discussion of hydrogel design principles for culturing immune cells within biomaterials.
- Analysis of progress in developing engineered tissues for drug screening.
Main Results:
- Engineered biomaterial scaffolds can replicate key tumor microenvironmental cues.
- Hydrogel-based systems offer a platform for culturing diverse immune cells in a tumor context.
- These advanced in vitro models show promise for more accurate preclinical drug assessment.
Conclusions:
- Biomaterial scaffolds represent a significant advancement for in vitro cancer research.
- Incorporating immune cells into engineered tissues can enhance the relevance of drug screening models.
- Precision oncological drug screening using engineered tissues may improve the translation of cancer therapies from lab to clinic.

