Advanced co-culture systems: Enhancing cancer research with organoid-immune models

Organoids are three-dimensional cell cultures derived from stem cells. These cultures offer an array of new opportunities for precision medicine and highly personalized cancer treatment, but the absence of a tumor microenvironment (TME), including appropriate immune cells and stromal cells, remains a key limitation of organoid technology.^1,2

Work to address the limitation is being undertaken, with the ongoing development of new strategies for the co-culture of tumor organoids and immune cells creating new routes for the study of specific cancer therapies.

Co-cultures assist the study of cellular interactions in the TME, highlighting novel therapeutic targets and helping facilitate biomarker and neoantigen discovery for vaccine development.³

Approaches to co-culture models

Co-culturing organoids and immune cells typically involves either expanding immune cells in tumoroids explanted from the patient or directly adding immune cells to organoid cultures.⁴

It should be noted, however, that no universal medium can accommodate both immune cells and organoids. It is necessary to perform detailed experiments before co-culture to ascertain the ideal organoid proliferation conditions without harming the immune cells themselves.³

Both organoid cultures and immune cells must contain certain cytokines and growth factors. For example, Wnt3a, EGF, Noggin, and R-spondin-1 form the most classical cytokine scheme in organoid cultures, while IL-2, IL-7, IL-15, and IL-21 are vital for immune cell cultures.⁵

Co-culture methods for tumor organoids and immune cells. (https://doi.org/ 10.1 186/s1 3046-023-02653-W)

Applications in cancer therapy

It is possible to employ co-culture models in studying the impact of immune cells on tumor growth, progression, and metastasis and when exploring the development of biomarkers and drug resistance mechanisms.²

Co-culture models also play a vital role in immunotherapy, particularly when evaluating and optimizing immunotherapy efficacy.

Introducing pathogens into co-culture systems allows cancer and inflammatory lesions to be simulated via pathogen-immune cell interactions, enabling the assessment of immunomodulation and immunotherapy responses.

These culture systems may also be used to study innate immune-promoting T-cell effector functions by including various types of immune cells.⁶

Research into co-culture models is ongoing, and work continues toward breakthroughs in cancer therapy.

Co-culturing peripheral blood lymphocytes with non-small cell lung cancer organoids can assist in acquiring patient-specific T cells, for example.⁷

Another example lies in the co-culture of dendritic cells with CD8+ T cells followed by co-culture with patient-derived gastric cancer organoids, a process which has the potential to predict precision medicine efficacy and lead to an improved prognosis for gastric cancer patients.⁸

Co-culturing CAR-derived cells (for example, CAR-T, CAR-NK, and CAR-M) and tumor organoids may also be sufficient to capture the molecular and cellular processes during immunotherapy. This development could become critical to identifying and selecting appropriate target antigens while offering excellent potential for predicting efficacy and toxicity assessments.⁹

Challenges and prospects

The co-culturing of tumor organoids with immune cells offers valuable models for precision cancer therapy, as this helps to bring three-dimensional organoid models closer to their in vivo state. This ever-evolving tool can improve the effectiveness of immunotherapy while advancing wider understanding of cancer research techniques.

Contemporary co-culture techniques exhibit some obvious limitations, however. Because each cell type requires a specific medium, co-culture conditions for organoids generally compromise the ideal conditions for each cell type.

The proliferation rate of co-cultured cells and the diffusion of cell-produced paracrine factors are influenced by the medium composition, meaning that achieving an optimal medium for the maturation and vascularization of organoids represents a particular challenge.¹⁰

Future co-culture research is anticipated to place additional emphasis on optimizing co-culture conditions, such as medium composition and the type of endothelial cell medium used. This additional research aims to ensure a more robust biological modeling platform for cancer research applications.

CiteAb named Sino Biological “Growth Factor Supplier to Watch in 2024.” The company offers a comprehensive suite of solutions for cancer immunotherapy, including tools for CAR-T therapy, CAR-NK therapy, and three-dimensional organoid research.

Sino Biological’s offering includes a diverse array of high-quality GMP- and RUO-grade cytokines and growth factors, each offering validated bioactivity, batch-to-batch consistency, and purity.

The company’s expertise, experience, and product range allow Sino Biological to continue to play a pivotal role in ensuring the optimal and consistent growth of organoids and immune cell cultures across the industry.

References and further reading

1. Zhao, J., Fong, A., Seow, S. V., & Toh, H. C. (2023). Organoids as an enabler of precision Immuno-oncology. Cells, 12(8), 1165.
2. Jeong, S. R., & Kang, M. (2023). Exploring Tumor–Immune Interactions in Co-Culture Models of T Cells and Tumor Organoids Derived from Patients. International Journal of Molecular Sciences, 24(19), 14609.
3. Magré, L., Verstegen, M. M., Buschow, S., van der Laan, L. J., Peppelenbosch, M., & Desai, J. (2023). Emerging organoid-immune co-culture models for cancer research: From oncoimmunology to personalized immunotherapies. Journal for Immunotherapy of Cancer, 11(5).
4. Bogoslowski, A., An, M., & Penninger, J. M. (2023). Incorporating Immune Cells into Organoid Models: Essential for Studying Human Disease. Organoids, 2(3), 140-155.
5. Sato, T., Stange, D. E., Ferrante, M., Vries, R. G., Van Es, J. H., Van Den Brink, S., & Clevers, H. (2011). Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium. Gastroenterology, 141(5), 1762-1772.
6. Yuki, K., Cheng, N., Nakano, M., & Kuo, C. J. (2020). Organoid models of tumor immunology. Trends in immunology, 41(8), 652-664.
7. Dijkstra, K. K., Cattaneo, C. M., Weeber, F., Chalabi, M., van de Haar, J., Fanchi, L. F., & Voest, E. E. (2018). Generation of tumor-reactive T cells by co-culture of peripheral blood lymphocytes and tumor organoids. Cell, 174(6), 1586-1598.
8. Chakrabarti, J., Koh, V., So, J. B. Y., Yong, W. P., & Zavros, Y. (2021). A preclinical human-derived autologous gastric cancer Organoid/Immune cell Co-culture model to predict the efficacy of targeted therapies. JoVE (Journal of Visualized Experiments), (173), e61443.
9. Yuan, J., Li, X., & Yu, S. (2023). Cancer organoid co-culture model system: Novel approach to guide precision medicine. Frontiers in Immunology, 13, 1061388.
10. Zahmatkesh, E., Khoshdel-Rad, N., Mirzaei, H., Shpichka, A., Timashev, P., Mahmoudi, T., & Vosough, M. (2021). Evolution of organoid technology: Lessons learnt in Co-Culture systems from developmental biology. Developmental biology, 475, 37-53.

Acknowledgments

Produced from materials originally authored by Sino Biological.

About Sino Biological Inc.

Sino Biological is an international reagent supplier and service provider. The company specializes in recombinant protein production and antibody development. All of Sino Biological’s products are independently developed and produced, including recombinant proteins, antibodies and cDNA clones. Sino Biological is the researchers’ one-stop technical services shop for the advanced technology platforms they need to make advancements. In addition, Sino Biological offer pharmaceutical companies and biotechnology firms pre-clinical production technology services for hundreds of monoclonal antibody drug candidates.

Sino Biological’s core business

Sino Biological is committed to providing high-quality recombinant protein and antibody reagents and to being a one-stop technical services shop for life science researchers around the world. All of our products are independently developed and produced. In addition, we offer pharmaceutical companies and biotechnology firms pre-clinical production technology services for hundreds of monoclonal antibody drug candidates. Our product quality control indicators meet rigorous requirements for clinical use samples. It takes only a few weeks for us to produce 1 to 30 grams of purified monoclonal antibody from gene sequencing.

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