Cutting-Edge Solutions to Streamline CAR-T R&D
Chimeric antigen receptor (CAR) T-cell therapy represents a major advancement in the fight against cancer and a paradigm shift toward personalized medicine. Although treatment with CAR-T cells has produced remarkable clinical responses within certain subsets of B-cell leukemia or lymphoma, many challenges limit the therapeutic efficacy of CAR-T cells in solid tumors.
This rapidly growing field faces several challenges, from basic research and early-stage clinical trials to Investigational New Drug (IND) applications and final product release. These challenges include comprehensive screening of the product as well as quality control testing to ensure patient safety.
Additional challenges in research and development of effective CAR-T cell therapies include:
Sartorius addresses these challenges with cutting-edge solutions that streamline lab-scale research and development workflows for characterizing quality attributes of T-cells.
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Before moving into late-stage clinical trials and submitting IND applications, multiple versions of the CAR-T cellular therapy product are evaluated in line with FDA guidance “Studying Multiple Versions of a Cellular or Gene Therapy Product in an Early-Phase Clinical Trial”. To ensure patient safety, both safety and bioactivity must be demonstrated for each product variant.
The Incucyte® Live-Cell Analysis and iQue® 3 High-Throughput Cytometry platforms support toxicology studies.
T-cell characterization and safety testing is required, not only for final release, but also as in-process testing at several stages throughout the discovery and development process.
These processes are often time-sensitive, so rapid solutions are important. Real-time screening and analysis solutions enable continuous phenotypic and functional analysis over time, while contaminant-free systems coupled with rapid testing options help ensure safety.
After clinical scale expansion, cells are harvested gently, concentrated and filled into single-use bags under strictly controlled environments.
Ensuring patient safety is paramount. Biosafety testing - including rapid microbial and fungal sterility and testing for mycoplasma - are crucial components of the comprehensive testing packages.
During the expansion stage, engineered CAR-T cells are cultured ex vivo in closed and automated bioreactor systems - such as Ambr® 15 Cell Culture and Ambr® 250 Modular - that enable rapid identification and optimization of critical process parameters and critical quality attributes (CQAs). The activation state, proliferation, viability and phenotype of the T-cell exhaustion - as well as memory and functional testing of killing capacity of T-cell population - are key CQAs closely monitored during this stage using the Incucyte® Live-Cell Analysis and iQue® 3 High-Throughput Cytometry platforms.
Cytokines, like interleukin-2 (IL-2) and interleukin (IL-7), support T-cell activation and expansion of desirable phenotypes.
Lentiviral vectors are the most commonly used to deliver various CAR constructs into immune cells. Our solutions for lab-scale workflows include:
Chimeric Antigen Receptors (CARs) are engineered to specifically target cancer cell antigens and enhance T-cell proliferation and cytotoxicity. Target specificity and T-cell lifecycle are key factors for therapeutic success. These can be measured with:
Different methods are available for T-cell activation (using primary and co-stimulatory signals), which can lead to different activation strengths. The ability to quantify activation profiles and characterize signaling pathways helps streamline the research process.
Assays that can support your research at this stage include:
Following isolation from a patient (autologous therapy) or donor (allogenic therapy), T cells must be carefully selected and enriched to increase cell count and improve product specificity. In vitro cell-based assays such as the iQue® Cell Count and Viability kit - as well as immune cell activation and proliferation - provide key insights for decision making.
Additionally, rapid sterility and mycoplasma testing of source material is a critical step in mitigating contamination risks.
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In vitro cell-based and protein interaction assays support early-phase CAR-T research and discovery
Measure biomarker phenotype, tri-lineage differentiation capacity, viability, exhaustion and killing efficacy with iQue® 3 and Incucyte® systems
Lab-scale lentivirus workflow and quality testing solutions
Analytical characterization and microbial safety testing are critical pillars of patient safety
The Incucyte® Live-Cell Analysis Platform enables real-time, live-cell analysis directly inside your incubator. Measure kinetic effects of your cell viability and characterize phenotypic or functional changes of CAR-T target cells without ever having to remove cells from the incubator. Incucyte® software makes the process of acquiring, viewing, analyzing and sharing images of living cells easier than ever before.
Related eBook: Harnessing the Power of T Cells
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The iQue® 3 is a high-throughput, suspension cell and bead analysis platform for rapidly profiling of immune-cell phenotype and function in therapeutic workflows. Ideal for those screens where cells are precious or limited in number, the iQue® 3 is the fastest way to generate high-content data from small samples.
1uL minimum sample volume requirement in a 384-well format, with zero dead volume. Cell detection occurs at rates of thousands of cells per second.
Related App Note: Combining Live-Cell Analysis and High-Throughput Flow Cytometry to Gain Additional Insights into the Mechanisms of Immune Cell Killing of Tumor Cells
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Octet®️ Label-Free Bio Layer Interferometry (BLI) technology uses optical biosensors to measure protein-protein interactions in parallel, without the use of detection agents. This robust and fluidics-free approach enables fast, real-time characterization of expressed proteins, even in complex and unpurified samples.
Related White Paper: Streamlining Affinity Analysis for Accelerated Lead Screening
The CellCelector Flex Platform is a fully automated cell imaging and picking system developed for screening, selection and isolation of single cells, clusters, spheroids, and organoids as well as single-cell clones and adherent colonies.
Related App Guide: Fully Automated Image-Based Single Cell and Colony Picking for Stem Cells
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Validated test results for Advanced Therapy Medicinal Products (ATMPs): Rapid bacteria and fungi detection in only 3 hours. The combination of speed, accuracy and efficiency provided by the Microsart®️ ATMP Sterile Release kits means ATMP manufacturers can deliver QC results prior to treatment. In doing so, the industry stands to eliminate one of the outstanding risks to patients posed by ATMP, thereby setting the stage for the use of consistently safe lifesaving cell-based therapies.
Related Infographic: Be on the Safe Side
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Streamlined workflows through collapsing of cell and biomolecule interaction analysis assays, validation of results by complementary technologies and robust multiparametric software analysis.
Obtain results for sterility in only three hours with real-time PCR Microsart® ATMP Sterile Release Kits.
Multifactorial results of high-content functional and phenotyping assays provide better insight into the desired characteristics of lead product variants, allowing confident selection of products to move forward.
Ensure patient safety through regular testing for microbial contaminants, including mycoplasma, bacteria and fungi throughout your research workflow. Microsart® real-time PCR assays provide rapid results within a few hours and need only a small number of precious samples from small batches.
This study investigates the expansion of T cells by comparing the growth and anti-cancer effects of serum-free and serum-containing media.
Watch this video to learn more about the steps and overcoming challenges in bringing a new CAR-T therapy to patients.
Learn about streamlined in vitro assays used for phenotyping and functional assessment of modified CAR-T cells, with three case studies.
View this inforgraphic to learn how CAR-T therapy works, the R&D workflow, and more.
The iQue® Human T Cell Activation and iQue® Human T Cell Killing kits are compatible with the iQue® 3 High-Throughput Cytometry Platform and can be used to characterize and monitor the function of T cells. Furthermore, other Qbeads/cytokines and immunophenotyping kits are available to help isolate T-cells and capture the secreted cytokines level using a high-throughput platform, in the same assay plate.
The Incucyte® Live-Cell Analysis system enables you to visualize and quantify immune cell interactions and proliferation in real time and automatically generate kinetics data of cell cultures. Scientists can investigate the mechanisms of immune cell activation (proliferation), regulation and differentiation (clustering) from inside the incubator and without the need to perturb or label cells.
The Incucyte® Live-Cell Analysis System and iQue® 3 High-Throughput Cytometry Platform can be used to evaluate and quantitate key functions of T cells, including activation and clustering, antibody internalization assays, chemotaxis, cytokine production and evaluation of complex co-culture models.
Using the Octet® Label-Free Bio-Layer Interferometry (BLI) Detection Systems, you can quantify and screen CAR-vector potency and access to target binding in cell therapy models and immune cell cultures.
The CellCelector Flex platform is a fully automated cell imaging and picking system developed for the screening, selection and isolation of single cells, clusters, spheroids and organoids, as well as single-cell clones and adherent colonies.
Detect bacterial and fungal contamination within three hours using the proven real-time PCR method in our Microsart® ATMP Sterile Release Kit, a combination of Microsart® ATMP Bacteria and of Microsart® ATMP Fungi.
Secure and configurable software module to track all system events and user actions.
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