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Tcr Technology - Creative Biolabs
- 1. TCR Technology A briefintroduction of engineered T cell for anti-tumor therapy
- 2. Cancer Immune Therapy:a glimpse CTLA-4, PD-1 Lymphocytes infiltrating into or surround tumors Capable of recognizing tumor associated antigen PBMC/PBL in vitro incubation with cytokines and other additions Stimulating the immune system to eliminate tumor cells. High affinity TCR gene transfer engineered T cell Antibody-TCR chimeric gene transfer engineered T cell Immunotherapy Adoptive cell transfer (ACT) Immune checkpoint inhibitor mAb drugs Tumor infiltrating lymphocytes (TILs) TCR engineered T cell (TCR-T) Cytokine induced killer cell (CIK) Chimeric antigen receptor T cell (CART)
- 3. APC T cell MHC I CD8 CD3CD3 Germline TCR α gene Germline TCR β gene Spliced TCR α mRNA Spliced TCR β mRNA TCR αβ heterodimer protein T Cell Receptor Engineered T cell: TCR structure TCR-MHC Complex Gene splice of TCR α&β domain
- 4. Development of engineeredT cells: TCR gene transfer Chose a Proper Antigen High Affinity T Cell Clone Isolation TCR α/β Gene Packaging Improving TCR Performance Adoptive Transfer into Patients Five Steps TCR-T Cell Development
- 5. High Affinity T Cell Receptor From autologous TILs From allogenicT cells From transgenic mice From phage library Natural T cell with anti-tumor specificity T cell from individual without TAA tolerance T cell from humanized mouse without TAA tolerance Phage display library screening High Affinity T Cell Clone Isolation
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- 7. Single andDual Amino Acid Substitutions in TCR CDRs Can Enhance Antigen-Specific T Cell Functions Murine-Human Hybrid TCR Preferential pairing reduce endogenous mispairing Increased stability of the TCR/CD3ζ Add a second disulfide bonds Add cysteines Use mouse TCR gene in human TCR TCR Performance Improving Improve TCR affinity Increase TCR expression Reduce mispairing TCR
- 8. Cancer Target Antigen Gene Vector Comments Reference Melanoma MART-1 TCR- RTV 30%response rate with on-target/off tumor toxicity Johnson et.al., 2009 Melanoma Gp100 TCR- RTV 19% response rate with on-target/off tumor toxicity Johnson et al., 2009 Colorectal Cancer CEA TCR- RTV Responses associated with on-target/off tumor toxicity Parkhurst et. al., 2010 Synovial Sarcoma and melanoma NY-ESO-1 TCR- RTV 50% response rate with no toxicity Robbins et.al., 2011 TCR Clinical Trial
- 9. Advantages Disadvantages They function throughwell- under-stood T-cell signaling pathways, and are the natural means by which the body clears foreign elements. The biology of the TCR restricts it to one HLA type and a/b TCRs cannot target nonprotein tumor antigens (i.e. carbo- hydrate or lipid antigens).
- 10. TCR Technology platform——CreativeBiolabs TCR-modified T Cells Construction TCR Validation TCR Application Clinical Applications TCR Construction Chimeric T Cell Receptors (chTCR) Murine-human Hybrid TCR TCR Gene Transfer Technologies TCR Transgene Expression Assay Lymphocyte Culture and Proliferation Assay Cytokines Release Assay TCR/CD3 Stability Assay TCR Pairing Lymphocyte Antigen Reactivity and Cytotoxicity Animal Experiments TCR Repertoire Sequencing TCR Vβ Repertoire Analysis MHC-peptide Tetramer TCR Clonality Assessment TCR Clonality Quantitation and CDR3 Size Diversity Technology TCR Clinical Diagnostics TCR Clinical Therapeutics
- 11. Address: 45-1 RamseyRoad, Shirley, NY 11967, USA Tel: 1-631-871-5806 Fax: 1-631-614-7828 Email: info@creative-biolabs.com Web: www.creative-biolabs.com/car-t/