• One-Stop CAR-T Therapy Development
  • Biomarker Identification & Selection
  • ScFv Generation
  • CAR Design & Construction
  • CAR-T Gene Packaging & Delivery
  • Replication-Competent Virus Testing
  • CAR Cell In Vitro Assay
  • CAR-T Preclinical In Vivo Assay
  • IND Development for CAR-T Cell Therapy
  • GMP Production for CAR-T Products
  • CAR Clinical Trial
  • One-Stop Canine CAR-T Therapy Development
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  • TRAC-CAR-T Cell Development
  • Modular CAR-T Cell Generation
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  • Vaccine Boosting CAR-T Cell Therapy
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  • CAR-T Therapy Development in the Non-Cancer Field
  • Anti-HIV CAR Cell Therapy Development
  • T Cell Activity Modulator Discovery
  • T Cell Programming
  • Virus Specific T Cell (VST) Development
  • Antibody-Coupled T Cell Receptor (ACTR) Development
  • Organoid-induced hPSC-original T Cell Differentiation
  • γδ T Cell Engineering
  • CAR-T CDMO
• One-Stop TCR-T Therapy Development
  • TCR Biomarker Identification & Selection
  • TCR Generation & Optimization
  • TCR Design & Construction
  • TCR Gene Packaging & Delivery
  • TCR In Vitro Assay
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• One-Stop CAR-MA Therapy Development
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  • One-Stop TCR-NK Therapy Development
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• One-Stop CAR-Monocyte Therapy Development
• One-Stop Cytokine Release Syndrome (CRS) Management
• TCR-Like Antibody Development
  • MHC/Peptide Complex Production
  • TCR-Like Antibody Discovery
  • TCR-Like Antibody Affinity Characterization
  • TCR-Like CAR Construction & Evaluation
• In Vivo Cell Engineering Development
  • In Vivo CAR-T Cell Engineering
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• One-Stop Allogeneic Cell Therapy Development
  • Allogeneic CAR-T Therapy Development
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• Immune Genotyping
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• Other Services
  • Tumor-infiltrating Lymphocyte-based Antibody Discovery

TCR Pairing Service

All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.

Creative Biolabs provides various techniques such as flow cytometry-based FRET, immunoprecipitation and western blotting for TCR pairing assay. Mispaired TCR heterodimers may result in the diluted expression of TCR transgene or the generation of autoreactive TCR, which affect the efficacy and safety of TCR engineered T cell therapy subsequently. It is a challenge to optimize TCR pairing issue.

Figure: TCR α- and β-chain pairing and mispairing. 1 and 2: pairing; 3 and 4: mispairing
(Disease Models & Mechanisms, 2015)

In the strategy of TCR-transfer, the modified T cells often have lower avidity than the parental T cells, which is one difficulty to achieve wild-type levels of TCR expression, resulting in limited efficacy. In order to solve the problem, the TCR chains should be initially selected for appropriate affinity and the vectors need to achieve and maintain high-level expression. Even these factors are met, there is also the possibility that the introduced exogenous TCR α and β chains assemble with the exogenous TCR αβ pairs, which decrease T cell avidity. Besides these, mismatched pairs may generate novel TCR pairs of undefined and have potentially self-reactive specificity. Various strategies have researched to facilitate TCR chains matched pairing. It is demonstrated that introducing cysteines residues into the constant region of TCRα and TCRβ chains can promote preferential pairing with each other, increase total surface expression of the introduced TCR chains, and reduce mismatching with endogenous TCR chains.

Moreover, we can evaluate TCR pairing and carry out optimized strategies to promote proper pairing by cell-based emulsion RT-PCR, generation of an exclusive TCR heterodimer, murine-human hybrid TCR or chimeric TCR. Our customer-oriented services are supplied to meet your requirement about TCR.

In the process to assess TCR pairing, flow cytometry-based FRET, immunoprecipitation and western blotting are generally used. Besides these classical methods, probes-based approach can also be developed. Based on the specific requirements of every client, scientists from Creative Biolabs can design and select appropriate strategies to assess TCR gene transfer.

References:

1. Michaela Sharpe and Natalie Mount. Genetically modified T cells in cancer therapy: opportunities and challenges. Dis Model Mech. 2015 Apr; 8(4):337-50.
2. Jürgen Kuball, et al. Facilitating matched pairing and expression of TCR chains introduced into human T cells. Blood. 2007 Mar 15;109(6):2331-8.
3. Minying Zhang, et al. A new approach to simultaneously quantify both TCR α- and β-chain diversity after adoptive immunotherapy.

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