• 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
  • One-Stop mRNA CAR-T Therapy Development
  • TRAC-CAR-T Cell Development
  • Modular CAR-T Cell Generation
  • One-Stop Silence™ CAR-T Cell Development
  • Vaccine Boosting CAR-T Cell Therapy
  • STAb-T Cell Therapy Development
  • 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
  • TCR-T Preclinical In Vivo Assay
  • TCR Clinical Application
  • TCR Analysis
  • TCR Tetramerization Construction
  • ScFv-TCR T Cell Therapy Development
  • AbTCR Development
  • Bispecific TCR Development
  • CER Development
• One-Stop CAR-MA Therapy Development
• One-Stop CAR-NK Therapy Development
  • One-Stop CAR-NKT Therapy Development
  • One-Stop UniCAR-NK Therapy Development
  • iPSC-derived CAR-NK Therapy Development
  • One-Stop TCR-NK Therapy Development
  • NK Cell Genetic Engineering
  • NK Cell Expansion
• One-Stop CAR-B Therapy Development
• 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
  • In Vivo B Cell Engineering
  • In Vivo CAR-NK Cell Engineering
  • In Vivo CAR-M Cell Engineering
• One-Stop Allogeneic Cell Therapy Development
  • Allogeneic CAR-T Therapy Development
  • Allogeneic TCR-T Therapy Development
  • Allogeneic CAR-NK Therapy Development
  • Allogeneic CAR/TCR Cell Design & Engineering
  • Other Allogeneic Cell Therapy Development
• TCR/CAR/Antigen-Engineered Tregs Development
  • CAR-Treg Development
• Cancer Vaccine Development
  • Cancer Vaccine Discovery
  • Cancer Vaccine Engineering
  • Cancer Vaccine Analytical Characterization
  • Cancer Vaccine In Vivo Assessment
  • Cancer Vaccine GMP Manufacturing
  • Dendritic Cell Vaccine Development
• Immune Genotyping
  • HLA Typing
  • KIR Typing
  • HLA Testing
  • Dog DLA Genotyping
  • Guinea Pig GPLA Genotyping
  • Mouse H2 Genotyping
  • Rabbit RLA Genotyping
  • Rat RT1 Genotyping
  • Rhesus Macaque MHC Genotyping
• Other Services
  • Tumor-infiltrating Lymphocyte-based Antibody Discovery

TCR-modified T Cell Construction Service

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

• TCR Construction
• Chimeric T Cell Receptors (chTCR)
• Murine-human Hybrid TCR
• TCR Gene Transfer Technologies

Altering the specificity of T cell receptor (TCR) is one of the popular strategies to genetically modify T cells for enhancing their tumor-killing activity. Creative Biolabs offers TCR-modified T cells construction services covering every unit, from epitope identification, TCR engineering to a series of validation assays.

T cells play a critical role in immunologic process. Hence, it is important to generate sufficient reactive T cells in the immunotherapies of many diseases. During cancer progression, immune system especially tumor-specific T cells may fail to eliminate cancer because of diverse reasons. The first class is intrinsic immune failure: (1) Tumor-specific T cells might be absent from the immune repertoire. The immune system is sculpted by the mechanisms of central and peripheral tolerance which make tumor-reactive T cells eliminated or only leave weakly tumor-reactive T cells. (2) Antigen-presenting cells (APCs) fail to present tumor-associated antigens in a form that is sufficiently antigenic for T cells, resulting in T cells can`t proliferate and persist in response to tumors. (3) Tumor-reactive immune cells do not localize to the tumor. (4) Regulatory T cells (CD4⁺CD25⁺FoxP3⁺) inhibit tumor-specific T-cell activity. Extrinsic immune evasion is another reason that is responsible for the failure of immune system to eliminate cancer. Tumors undergo a process of immunoediting during their development and growth. (1) Antigens, the peptide itself or combined with MHC molecules, might be down-regulated under immune-selection pressure. (2) Tumor cells or stromal elements can secret various factors to inhibit immune cells or bias the effector type produced. (3) Death-receptor pathways are down-regulated. Death receptors or their downstream signaling molecules might be mutated or lost entirely. So in order to induce effective immune responses, the effective immune response of specific T cells is the most important issue. There are two classical approaches to manipulate T-cell specificity: modification using TCR genes or modification using antibody genes. The former method usually refers to TCR-modified T cells. While the latter method utilizes genes encoding monoclonal antibody chains specific to tumor associated antigens. During the past decades, the strategy to modify T cells through altering the specificity of the TCR has made important advances. To construct TCR-modified T cells, genes encoding the α- and β-chains of TCR are isolated from T cells that are reactive to tumors and then transduce T cells or their precursors. Such TCR-modified T cells have been used in clinic and shown reactivity to tumor cells in vitro, induce antitumor effects in vivo. Based on the factors mentioned above, the T-cell genetic-modification strategies have also been expanded: tranducing T cells with a gene encoding a chimeric receptor that contains co-stimulatory domains; genes encoding growth factos, genes encoding chemokine receptors, suicide genes; transducing heamatopoietic stem cells with TCRs; infecting T cells with retrovirus; using dual-specific T cells; using T cells as APCs; using anti-apoptotic strategies; transducing T cells with; inducing resistance to tumor-derived inhibitory factors, etc.  

With advanced technologies and qualified groups, we can provide services for every client seeking for high-quality and cost-effective TCR-modified T cells solution for the scientific research. Our project manager teams can design and perform TCR-modified T cells construction to meet your request.

Reference:

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. Michael H. Kershaw, et al. Supernatural T cells: genetic modification of T cells for cancer therapy. Nat Rev Immunol. 2005 Dec;5(12):928-40.

To discuss your demands or to request a proposal, please contact us by .