Engineering soluble T‐cell receptors for therapy
| Autor: | David K. Cole, Catriona McMurran, Michelle L. McCully, Ross A. Robinson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
T‐cell receptor affinity‐enhanced bispecific T‐cell engagers medicine.medical_treatment Receptors Antigen T-Cell Human leukocyte antigen Protein Engineering Biochemistry 03 medical and health sciences 0302 clinical medicine Cancer immunotherapy Antigens Neoplasm medicine State‐of‐the‐Art Review Animals Humans Receptor Molecular Biology peptide–human leukocyte antigen State‐of‐the‐Art Reviews cancer immunotherapy Chemistry T-cell receptor Cell Biology Immunotherapy Protein engineering Ligand (biochemistry) Cell biology 030104 developmental biology Drug development 030220 oncology & carcinogenesis Protein Binding |
| Zdroj: | The Febs Journal |
| ISSN: | 1742-4658 1742-464X |
| Popis: | Immunotherapy approaches that target peptide–human leukocyte antigen (pHLA) complexes are becoming highly attractive because of their potential to access virtually all foreign and cellular proteins. For this reason, there has been considerable interest in the development of the natural ligand for pHLA, the T‐cell receptor (TCR), as a soluble drug to target disease‐associated pHLA presented at the cell surface. However, native TCR stability is suboptimal for soluble drug development, and natural TCRs generally have weak affinities for pHLAs, limiting their potential to reach efficacious receptor occupancy levels as soluble drugs. To overcome these limitations and make full use of the TCR as a soluble drug platform, several protein engineering solutions have been applied to TCRs to enhance both their stability and affinity, with a focus on retaining target specificity and selectivity. Here, we review these advances and look to the future for the next generation of soluble TCR‐based therapies that can target monomorphic HLA‐like proteins presenting both peptide and nonpeptide antigens. Native TCR stability and affinity are suboptimal for soluble drug development, limiting their potential as soluble drugs. To overcome these limitations and make full use of the TCR as a soluble drug platform, several protein engineering solutions have been applied to TCRs to enhance both their stability and affinity, with a focus on retaining target specificity and selectivity. |
| Databáze: | OpenAIRE |
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