Extensive functional comparisons between chimeric antigen receptors and T cell receptors highlight fundamental similarities
| Autor: | Mark L. Sandberg, Yuta Ando, Alexander Kamb, Ming-Lun Wu, Kathleen R Negri, Wen-Hua Lee, Julyun Oh, Xueyin Wang, Michele McElvain, Grant B Gabrelow, Aaron D. Martin, Han Xu, Dora Toledo Warshaviak |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Receptors
Chimeric Antigen T-Lymphocytes T cell Immunology T-cell receptor Receptors Antigen T-Cell hemic and immune systems chemical and pharmacologic phenomena Context (language use) Biology Lymphocyte Activation Chimeric antigen receptor Immune system medicine.anatomical_structure medicine Humans Receptor Molecular Biology Neuroscience CD80 Function (biology) |
| Zdroj: | Molecular Immunology. 138:137-149 |
| ISSN: | 0161-5890 |
| DOI: | 10.1016/j.molimm.2021.07.018 |
| Popis: | Though TCRs have been subject to limited engineering in the context of therapeutic design and optimization, they are used largely as found in nature. On the other hand, CARs are artificial, composed of different segments of proteins that function in the immune system. This characteristic raises the possibility of altered response to immune regulatory stimuli. Here we describe a large-scale, systematic comparison of CARs and TCRs across 5 different pMHC targets, with a total of 19 constructs examined in vitro. These functional measurements include CAR- and TCR-mediated activation, proliferation, and cytotoxicity in both acute and chronic settings. Surprisingly, we find no consistent difference between CARs and TCRs as receptor classes with respect to their relative sensitivity to major regulators of T cell activation: PD-L1, CD80/86 and IL-2. Though TCRs often emerge from human blood directly as potent, selective receptors, CARs must be heavily optimized to attain these properties for pMHC targets. Nonetheless, when iteratively improved and compared head to head in functional tests, CARs appear remarkably similar to TCRs with respect to immune modulation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect