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Quantitative In Vivo Bioanalysis | Quantitative Cell Persistence | Multiparameter Subpopulation Analysis | Recombinant Anti-Idiotypic Antibody Services | Resources |
Elucidate the Body’s Response to Your Cell Therapy
Assess the body’s reaction to your cell therapy by developing in vivo bioanalysis assays to monitor CAR T-cell persistence, exhaustion, and other functional parameters.
Generate In Vivo Insight Through Quantitative In Vitro Assays
Your focus on in vitro development can mean nothing if the body manages to inactivate the therapeutic. For solid tumor-focused T-cell therapies, persistence is a persistent problem. The immunosuppressive tumor microenvironment (TME) is a tough barrier to prevail against, not to mention loss of functionality due to T-cell exhaustion.
Additionally, regardless of the type of cell therapy you are developing, you need to be sure that your therapeutic has a safe and effective bioavailability and tissue distribution profile.
While we eagerly wait for your innovations on improving CAR T-cell persistence to come to the market, we can accelerate your path to that goal with efficient and quantitatively accurate tools for developing and deploying in vivo bioanalysis assays.
Did you know?
The concept of digital PCR was first described in 1992 by Sykes, et al.,1 who recognized that the combination of limiting dilution, end-point PCR, and Poisson statistics could yield an absolute measure of nucleic acid concentration.
Quantify CAR T-Cell Persistence with Droplet Digital™ PCR (ddPCR™)
When you are monitoring in vivo engraftment, expansion, and persistence of your cell therapy, quantifying the presence of your transgene can provide a highly accurate, sensitive, and reproducible measurement — exactly the type of assay where ddPCR excels.
With ddPCR, quantification does not depend on amplification efficiency but instead uses endpoint PCR to deliver absolute measurement. The process starts by isolating individual transgenes from your sample into discrete, volumetrically defined droplet partitions. Then, inside each partition, the nucleic acid is amplified if the transgene is present. Quantification is determined by calculating the ratio of transgene-positive partitions to transgene-negative partitions.
Transgene measurement with ddPCR is precise and accurate, and with our family of ddPCR instruments, straightforward to learn and implement.
Browse ddPCR Assays for Your Viral Vector Characterization Needs
Multiplex Mutation
Screening
Residual DNA
Quantification
Copy Number
Genome Edit
Detection
Mutation
Detection
Copy Number
Determination
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Introduction to Digital PCR
New to ddPCR technology? Learn more here.
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PCR Qualitative
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Real-Time PCR Relative Quantitation
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Droplet Digital PCR Absolute Quantitation
Monitor Critical Cell Subpopulations with Multi-Parameter Flow Cytometry
When you need more context around the persistence, bioavailability, and distribution of your cell therapy and/or would like to monitor the effects of your cell therapy on cell subpopulations, flow cytometry is an obvious choice. But conventional flow cytometry can be time-consuming and manual.
Bio-Rad introduces efficiency into your multi-parameter flow cytometry studies with the high-performance, automation-ready ZE5 Cell Analyzer. You can quickly obtain the deep level of information you need to assess discrete immune cell populations.
- Distinguish T cells during isolation and activation
- Evaluate CAR expression on functional T cells
- Monitor CAR T-cell potency and specificity
FEATURED DOCUMENTMonitoring T-Cell Exhaustion After IMT
Read how the multi-parametric capability of the ZE5 Cell Analyzer enables monitoring of T-cell exhaustion after Nivolumab treatment.
Detect and Differentiate Your Modified Cells with Custom Antibodies
High-quality antibody reagents are vital for accurate detection, quantification, and tracking of CAR T cells or other genetically modified cells in preclinical models and clinical studies. To ensure continued availability and consistent performance of these critical reagents, recombinant antibody technology is ideal.
Bio-Rad’s custom recombinant anti-idiotypic antibody services can generate the specific antibodies you need for cellular kinetics, T-cell enrichment, and immunophenotyping. Our in vitro antibody phage display and SpyTag technology produces recombinant antibodies in multiple formats in less than 3 months and can be used in a range of applications. Since these highly-specialized reagents are recombinantly produced, you get a secure supply for clinical trials and beyond.
Resources
Publications
Accurate In-Vivo Quantification of CD19 CAR-T Cells after Treatment with Axicabtagene Ciloleucel (Axi-Cel) and Tisagenlecleucel (Tisa-Cel) Using Digital PCR
Badbaran A, et al. Cancers (Basel). 2020 Jul 20;12(7):1970. doi: 10.3390/cancers12071970.
Insights on Droplet Digital PCR–Based Cellular Kinetics and Biodistribution Assay Support for CAR-T Cell Therapy
Sugimoto H, et al. AAPS J. 2021 Mar 2;23(2):36. doi: 10.1208/s12248-021-00560-6.
Documents
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Utilizing the Multi-Parameter Capability of the ZE5 Cell Analyzer to Monitor T-Cell Exhaustion Following Immunotherapy
Discover how to utilize the multi-parameter capability of the ZE5 Flow Cytometer to monitor T-cell exhaustion following immunotherapy.
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Counting Genetically Modified Cells Using Whole Cell-Based Droplet Digital™ PCR
Count modified cells using ddPCR technology by encapsulating whole cells and targeting the transgene and reference gene to amplify DNA within.
References
- Sykes PJ, et al. Quantitation of targets for PCR by use of limiting dilution. Biotechniques. 1992 Sep;13(3):444-9.
Discover More Cell Therapy Development Solutions
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Cell Therapy Development Overview
Creating standardized treatments from inherently variable material like living cells requires knowing exactly what you are working with, whether in discovery, development, or manufacturing. Bio-Rad is here to help.
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Antigen Discovery
Discover innovative cell therapy approaches quickly and confidently with automated and quantitative tools for neoantigen discovery, CAR T-cell characterization, CAR construct optimization, and more.
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Characterization
Develop critical assays to evaluate potency and batch-to-batch consistency, whether for CAR T-cell characterization or development of another cell therapy approach.
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Manufacturing & QC
Efficiently ensure the safety of your cell therapy manufacturing process, whether you are evaluating transgene copy number or verifying the absence of microbial pathogens.