An Automatable Hydrogel Culture Platform for Evaluating Efficacy of Antibody-Based Therapeutics in Overcoming Chemoresistance
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Updated: Dec 29, 2025
Hydrogel Arrays Enable Increased Throughput for Screening Effects of Matrix Components and Therapeutics in 3D Tumor Models
Published on: June 16, 2022
Anna Kletzmayr1,2, Flurina Clement Frey1, Miriam Zimmermann1
1CellSpring AG, ETH Zürich ieLab, Zürich, Switzerland.
Abstract:
The microenvironment plays a major role in conferring chemoresistance to cancer cells. In order to better inform clinical response to chemoresistance, preclinical models that recapitulate its hallmark features are needed to enable screening for resistance-specific therapeutic targets. A novel platform for seeding cancer cells in 3D hydrogels is presented utilizing derivatives of chitosan and alginate that, critically, is amenable to high throughput screening: cell seeding in hydrogels, media changes, dosing of anticancer compounds, and cell viability assays are all automated using a standard and commercially available liquid handling robot. Culture in these hydrogels elicits resistance in ovarian, lung, and prostate cancer cells to treatment by doxorubicin and paclitaxel. In correlation, proteomics analysis of SKOV3 cells cultured in 3D reveals enrichment of proteins associated with extreme drug resistance including HMOX1 and ALDH2. Subsequently, therapeutic antibodies targeted to tumor-associated antigens upregulated in 3D cultures are shown to have higher efficacy compared to 2D cultures. Collectively, this automated 3D cell culture platform provides a powerful tool with utility in identification of drugs that may overcome chemoresistance.
Insights
A new automated 3D hydrogel platform using chitosan and alginate can screen for cancer chemoresistance. This model helps identify new therapies to overcome drug resistance in ovarian, lung, and prostate cancers.
Area of Science:
- Biotechnology
- Cancer Research
- Drug Discovery
Background:
- The tumor microenvironment significantly influences cancer cell chemoresistance.
- Preclinical models are crucial for identifying therapeutic targets against chemoresistance.
- Existing models often fail to fully recapitulate the complex tumor microenvironment.
Purpose of the Study:
- To develop and validate a novel, high-throughput 3D hydrogel platform for studying cancer chemoresistance.
- To assess the platform's ability to elicit chemoresistance in various cancer cell types.
- To evaluate the efficacy of targeted therapies in this 3D model.
Main Methods:
- Utilized chitosan and alginate derivatives to create 3D hydrogels for cancer cell culture.
- Automated cell seeding, media changes, drug dosing, and viability assays using a liquid handling robot.
- Performed proteomic analysis on cells cultured in 3D versus 2D conditions.
- Tested therapeutic antibodies targeting upregulated antigens in 3D cultures.
Main Results:
- The 3D hydrogel platform successfully induced chemoresistance in ovarian, lung, and prostate cancer cells against doxorubicin and paclitaxel.
- Proteomic analysis revealed enrichment of drug resistance-associated proteins (e.g., HMOX1, ALDH2) in 3D cultured cells.
- Therapeutic antibodies showed enhanced efficacy against cancer cells in 3D cultures compared to 2D cultures.
Conclusions:
- The automated 3D hydrogel platform effectively models cancer chemoresistance.
- This platform facilitates high-throughput screening for novel therapeutic targets and drugs to overcome chemoresistance.
- The findings support the development of targeted therapies based on 3D culture-identified biomarkers.
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