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3 minute read
Did you know that 3D organ-like tumor models are biomimetic and yield superior results in drug screening? These models more accurately mimic cell-cell signaling and physiological conditions, providing a superior representation of human tumors outside the body. This blog is dedicated to answering frequently asked questions about Champion's advanced TumorGraft3D platform and assisting scientists in choosing the right platform for their drug screening endeavors.
Champions Oncology offers the multiclonal TumorGraft3D drug screening platform, a biologically relevant platform with 3D organoid models derived from our superior, well-characterized patient-derived xenografts (PDXs) for ex vivo drug testing.
1) What is TumorGraft3D and what differentiates them from conventional 3D models?
TumorGraft3D models are self-organizing three-dimensional PDX-derived cell clusters that mimic parental human tumor's morphological and molecular phenotype, thereby rendering themselves clinically relevant models for drug discovery.
2) What types of TumorGraft3D models are currently available?
Our TumorGraft3D biobank is constantly expanding and currently includes over 150 off-the-shelf models across 16 different tumor types for ex vivo studies. However, our entire PDX bank is available for TumorGraft3D generation, only requiring a short pre-study development phase before becoming available for clients’ studies.
3) What are the advantages of using TumorGraft3D models compared to cell lines or in vivo PDX studies?
TumorGraft3D models are generated from our deeply characterized and clinically annotated patient-derived xenograft models and maintain the parent model’s characteristics. They represent the heterogeneity of the patient population and have drug response profiles comparable to the parent PDX model. This makes them a great resource for ex vivo drug screening, with better clinical correlation than cell lines, and have a faster turnaround time and higher throughput than in vivo studies.
4) Are TumorGraft3D models a close representation of patients’ tumors? How do you ensure that patients' characteristics are not lost?
TumorGraft3D models are derived from our PDX models without intermediate processing steps and are maintained at low passages to avoid genetic drift and preserve the parent PDX model characteristics. Moreover, IHC, NGS, and drug response analysis are conducted to characterize the TumorGraft3D model and verify that this maintains the parent PDX model’s molecular and pharmacological profile.
5) Why do you use a matrix-free assay? What are the advantages and disadvantages of it?
Traditionally, 3D tissue models have been cultured using an extracellular matrix-dependent approach, where the supportive extracellular matrix is derived from natural or synthetic sources. Matrices can pose several challenges such as sourcing of materials, interactions with test agents, and interference in imaging-relevant readouts. Matrix-free approaches allow the end user to observe the self-organization of 3D tissue models without using an exogenous matrix, circumventing all the above challenges. A matrix-free environment allows homogeneous distribution of therapeutic agents and easy access to tumor and immune cells. Additionally, the absence of confounding factors simplifies the assay readout and reduces variability. The use of an exogenous matrix can mimic the physical characteristics of the TME but can also influence tumor cell behavior and it interferes with flow cytometry readouts.
6) How can I use TumorGraft3D to study the TME and agents targeting/engaging the TME?
TumorGraft3D models are a well-defined versatile platform that lends itself to various co-culture options and readouts that can generate a complete picture of the TME response to test agents. At Champions, we offer co-culture assays with autologous and allogeneic NK cells, PBMCs, TILs, and other immune cells, allowing for testing of several classes of therapeutic agents such as T cell and NK cell engagers, BiTEs, ADCC drugs, immune checkpoint inhibitors, small molecules, gene therapy, cell therapy, and combinatorial therapy.
7) What are the applications of TumorGraft3D? How can I use this platform to advance my oncology research program?
TumorGraft3D models' versatility and clinical relevance, along with their molecular characterization, make them the ideal ex vivo models to measure agent efficacy and on-target effect, unravel the complexities of tumor biology and the crucial interactions within the tumor microenvironment, and evaluate synergistic combination therapies to de-risk in vivo studies through data-driven decisions.
8) How does Champions Oncology ensure the quality of your 3D tumor models?
At Champions, we strive to provide the highest quality services. Our TumorGraft3D models are carefully developed following cutting-edge guidelines for organoid development and culture. Our models are:
• maintained at low passages to retain molecular and phenotypic characteristics,
• qualified for assays using predefined SOC compounds,
• verified for true 3D structure formation and viability throughout the length of the assay.
9) What is unique about the TumorGraft3D platform?
Specially tailored for integration with various immune cell types, TumorGraft3D models incorporate the unparalleled advantage of Champions’ proprietary autologous systems. Our proprietary autologous co-culture systems proficiently examine the potency of therapeutic agents alongside the intricate interactions between a patient's tumor and their own immune system. This advancement eliminates the inconsistencies commonly seen with the use of allogeneic donors, directing the focus onto patient-specific responses. Our clinically relevant models, coupled with advanced high-content imaging and flow cytometry immunophenotyping make our platform a rich source of insights.
With unprecedented precision, scientists can now:
• monitor the influence of test agents on the interaction between tumors and their microenvironment,
• decrypt their mechanisms of action,
• meticulously track the infiltration of immune cells,
• and craft potent combination therapies tailored for IO applications.
