TCR Generation and Optimization
To increase efficiency and accelerate drug discovery and development, Creative Biolabs offers comprehensive TCR engineering T cell early development services. The one-stop TCR engineering T cell development service process includes TCR biomarker identification and selection, TCR generation and optimization, design and construction, TCR gene packaging and delivery, TCR in vitro validation, and TCR-T pre-clinical in vivo animal testing. In particular, the generation and optimization of TCR is a key step in the development of TCR, and the optimization strategy can be tailored to your specific needs.
TCR Generation
Creative Biolabs can use genetic engineering techniques to insert different functional TCR-encoding genes into T cells, making them specifically reactive to tumors. Our experienced team can provide you with a wide range of TCRs specifically for more tumor cell type antigens:
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TCR generated from patient's TILs
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TCR generated from phage display
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TCR generated from in vivo system
➢ TCR Optimization
Optimizing the affinity
The term affinity is used when referring to the binding strength of a TCR to an MHC/peptide complex. To increase the affinity of the TCR, yeast or phage displays has been successfully used to screen for random mutations. In addition, TCR with higher affinity can be identified by targeting mutations in the CDR3 region and screened for variants after transfection into T cells.
Optimizing the avidity
The term avidity is used when referring to the sum of all bindings between T cells and antigen presenting cells. Several strategies have been developed to increase the affinity of transduced T cells by increasing TCR levels on the cell surface:
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An improved gene transfer system (based on retroviral vector)
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Optimization of TCR-encoding nucleotide sequences (codon optimization)
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Molecular design of the TCR interface
Overview of Different TCR Optimization Strategies
Optimization Strategies
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Improved Functions
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in vitro evolution
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increased affinity
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codon optimization
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higher protein levels, no changes of amino acid sequence
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maturation
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preferential pairing, improved functional avidity
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additional disulfide bond
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preferential pairing, improved functional avidity
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amino acid exchanges between TCR and TCR
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slightly reduced mispairing
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For more details, please feel free to contact us for project quotations and more detailed information.
For Research Use Only | Not For Clinical Use