Patient-derived Organoids for Cell Therapy Development: The Needs Behind the Innovation

October 30, 2025

Advances in human-relevant disease models have reshaped early-stage drug discovery, but the development of cell therapies demands even more sophisticated platforms due to their increased complexity and stringent requirements.^1,2

Some cell-based therapies, such as CAR-T, involve living cells with characteristics that include proliferation, persistence, and tumor-targeting activity, that depend heavily on the surrounding biological environment. Conventional models cannot fully replicate these context-dependent dynamics. Accurately predicting cell therapy performance, therefore requires not only replicating the disease but also recreating the complex tissue microenvironments in which these therapies operate.

Patient-derived organoids (PDOs) chave emerged as powerful mechanistic disease models to meet these challenges, providing 3D platforms that preserve patient tumor architecture, genetics, and heterogeneity PDOs enable researchers to simulate tumor growth, evaluate cell therapy dosing, and personalize preclinical testing, thereby reducing risks before clinical trials.^3,4 In this article, we’ll explore how PDOs address essential needs in cell therapy development by providing robust and predictive disease models that enhance drug testing.

Capturing complexity with human-relevant modules

Cell therapies encounter biological complexities far beyond typical drug-target interactions, including tumor accessibility, immune evasion, and microenvironmental effects on cell survival and expansion. Understanding these factors requires advanced, robust disease models.

While patient-derived xenografts (PDXs) have long been the gold standard for human-relevant models, they are costly, slow to establish, and difficult to scale.^5,6 The Japanese Collection of Research Bioresources (JCRB) Cell Bank has further accelerated oncology research by offering a wide range of well-characterized cancer cell lines, serving as reliable workhorse tools for studying cancer biology and testing therapeutic candidates. Yet, even the most robust cell lines cannot capture the architectural complexity and patient-specific heterogeneity needed to predict CART-T efficacy. This limitation underscores the value of PDOs which address these gaps by offering faster, scalable platforms that preserve the genetic and histological features of real tumors.^3,4

Decoding tumor-immune interactions

PDOs maintain the 3D architecture, mutational profile, and heterogeneity of patient tumors, enabling researchers to study tumor-immune interactions with greater fidelity.^6,7 Unlike conventional 2D cultures, PDOs allow monitoring of CAR-T cell expansion, infiltration, and resistance in real-time. This creates opportunities to observe how immune cells adapt and how tumors evade, providing mechanistic insights that inform therapy optimization before clinical testing.⁸

Fine-tuning CAR-T dosing for safety and efficacy

Determining the correct dose for CAR-T therapies requires a balance between potency and the risk of triggering severe immune reactions. PDOs provide a controlled, human-relevant platform for exploring dose-response relationships and cytotoxicity thresholds.

For example, colorectal cancer PDOs have been used to assess CAR-T cytotoxicity in a realistic, 3D structure, showing how tumor architecture influences penetration and killing efficiency.¹⁰ Similarly, glioblastoma PDO models demonstrate patient-specific CAR-T responses, supporting more refined dosing and targeting strategies.^9,11

Tailoring cell therapy to individual patients

Every tumor and every patient responds differently to cell therapy. PDOs make it possible to move beyond genomic profiling by functionally testing therapies in patient-specific models.⁷

Another example, glioblastoma PDOs have revealed clonal heterogeneity and subpopulations with distinct drug sensitives, explaining why some patients despite initial treatment success.⁹ By capturing these dynamics, PDOs help guide more personalized treatment strategies and inform combination therapies that overcome resistance.

Advancing predictive, next-generation models

PDO research is evolving rapidly, serving as both a discovery tool and a preclinical platform. A 2025 study demonstrated glioblastoma PDOs that function as “avatars” to assess real-time CAR-T outcomes, bridging laboratory information with patient responses.¹¹

Future approaches aim to enhance physiological relevance by integrating PDOs with stromal and immune components through co-culture systems, or by combining them with iPSC-derived cells and organ-on-a-chip technologies. These advancements promise greater predictive accuracy while keeping systems practical for researchers.²

Bridging cell therapy and organoid research with FUJIFILM Biosciences solutions

As PDO models grow more complex, reliable workflows become essential for maintaining organoid viability and generating reproducible results. Equally important is the ability to connect PDO research to broader cell therapy development. FUJIFILM Biosciences supports both sides of this equation. Our cell therapy solutions provide optimized tools for handling, delivering, and characterizing therapeutic cells, ensuring quality and consistency throughout development. On the PDO side, tools such as the Shenandoah Recombinant Proteins strengthen organoid growth and longevity, preserving architecture and heterogeneity over time.

Together, these solutions create a bridge between cell therapy and organoid research, enabling researchers to generate more reliable human-relevant data that advances the field of CAR-T therapy. Researchers can also visit our disease modeling page to explore iPSC-based models that complement PDO studies and enhance preclinical research.

Looking ahead: PDO models advancing cell therapy development

The shift toward patient-derived organoids reflects the growing need for human-relevant, mechanistic disease models in cell therapy drug testing. PDOs offer a unique opportunity to capture tumor complexity, optimize dosing, and personalize preclinical evaluation, which are key steps for improving therapy predictability prior to clinical trials.

With ongoing advancements in co-culture systems, organ-on-a-chip integration, and dependable workflows supported by FUJIFILM Biosciences solutions, researchers can adopt PDO models with increased confidence and consistency. As these platforms become more accessible and physiologically accurate, PDOs are positioned to play a central role in the future of cell therapy development.

Stay tuned for the next article in this series, where we will explore more emerging trending trends in disease modeling. Subscribe to our mailing list for updates and follow us on LinkedIn to join the conversation.

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References:

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10. Schnalzger TE, de Groot MH, Zhang C, Mosa MH, Michels BE, Röder J, et al. (2019). 3D model for CAR-mediated cytotoxicity using patient-derived colorectal cancer organoids. EMBO J; 38(12): e100928.
11. Logun M, Wang X, Sun Y, Bagley SJ, Li N, Desai A, et al. (2025). Patient-derived glioblastoma organoids as real-time avatars for assessing responses to clinical CAR-T cell therapy. Cell Stem Cell; 32(2): 181-190.