Natural Receptor- and Ligand-Based Chimeric Antigen Receptors: Strategies Using Natural Ligands and Receptors for Targeted Cell Killing
Chimeric antigen receptor (CAR) T-cell therapy has been widely successful in the treatment of B-cell malignancies, including B-cell lymphoma, mantle cell lymphoma, and multiple myeloma; and three generations of CAR designs have led to effective FDA approved therapeutics. Traditionally, CAR antigen s...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/1/21 |
| _version_ | 1827668648822571008 |
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| author | Gianna M. Branella Harold Trent Spencer |
| author_facet | Gianna M. Branella Harold Trent Spencer |
| author_sort | Gianna M. Branella |
| collection | DOAJ |
| description | Chimeric antigen receptor (CAR) T-cell therapy has been widely successful in the treatment of B-cell malignancies, including B-cell lymphoma, mantle cell lymphoma, and multiple myeloma; and three generations of CAR designs have led to effective FDA approved therapeutics. Traditionally, CAR antigen specificity is derived from a monoclonal antibody where the variable heavy (V<sub>H</sub>) and variable light (V<sub>L</sub>) chains are connected by a peptide linker to form a single-chain variable fragment (scFv). While this provides a level of antigen specificity parallel to that of an antibody and has shown great success in the clinic, this design is not universally successful. For instance, issues of stability, immunogenicity, and antigen escape hinder the translational application of some CARs. As an alternative, natural receptor- or ligand-based designs may prove advantageous in some circumstances compared to scFv-based designs. Herein, the advantages and disadvantages of scFv-based and natural receptor- or ligand-based CAR designs are discussed. In addition, several translational aspects of natural receptor- and ligand-based CAR approaches that are being investigated in preclinical and clinical studies will be examined. |
| first_indexed | 2024-03-10T03:46:39Z |
| format | Article |
| id | doaj.art-b6587b8b926b46e18199ebb424eb48b5 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T03:46:39Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-b6587b8b926b46e18199ebb424eb48b52023-11-23T11:18:59ZengMDPI AGCells2073-44092021-12-011112110.3390/cells11010021Natural Receptor- and Ligand-Based Chimeric Antigen Receptors: Strategies Using Natural Ligands and Receptors for Targeted Cell KillingGianna M. Branella0Harold Trent Spencer1Aflac Cancer and Blood Disorders Center, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA 30322, USAAflac Cancer and Blood Disorders Center, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA 30322, USAChimeric antigen receptor (CAR) T-cell therapy has been widely successful in the treatment of B-cell malignancies, including B-cell lymphoma, mantle cell lymphoma, and multiple myeloma; and three generations of CAR designs have led to effective FDA approved therapeutics. Traditionally, CAR antigen specificity is derived from a monoclonal antibody where the variable heavy (V<sub>H</sub>) and variable light (V<sub>L</sub>) chains are connected by a peptide linker to form a single-chain variable fragment (scFv). While this provides a level of antigen specificity parallel to that of an antibody and has shown great success in the clinic, this design is not universally successful. For instance, issues of stability, immunogenicity, and antigen escape hinder the translational application of some CARs. As an alternative, natural receptor- or ligand-based designs may prove advantageous in some circumstances compared to scFv-based designs. Herein, the advantages and disadvantages of scFv-based and natural receptor- or ligand-based CAR designs are discussed. In addition, several translational aspects of natural receptor- and ligand-based CAR approaches that are being investigated in preclinical and clinical studies will be examined.https://www.mdpi.com/2073-4409/11/1/21chimeric antigen receptorCARligand-based CARnatural receptor-based CARimmunotherapycell therapy |
| spellingShingle | Gianna M. Branella Harold Trent Spencer Natural Receptor- and Ligand-Based Chimeric Antigen Receptors: Strategies Using Natural Ligands and Receptors for Targeted Cell Killing Cells chimeric antigen receptor CAR ligand-based CAR natural receptor-based CAR immunotherapy cell therapy |
| title | Natural Receptor- and Ligand-Based Chimeric Antigen Receptors: Strategies Using Natural Ligands and Receptors for Targeted Cell Killing |
| title_full | Natural Receptor- and Ligand-Based Chimeric Antigen Receptors: Strategies Using Natural Ligands and Receptors for Targeted Cell Killing |
| title_fullStr | Natural Receptor- and Ligand-Based Chimeric Antigen Receptors: Strategies Using Natural Ligands and Receptors for Targeted Cell Killing |
| title_full_unstemmed | Natural Receptor- and Ligand-Based Chimeric Antigen Receptors: Strategies Using Natural Ligands and Receptors for Targeted Cell Killing |
| title_short | Natural Receptor- and Ligand-Based Chimeric Antigen Receptors: Strategies Using Natural Ligands and Receptors for Targeted Cell Killing |
| title_sort | natural receptor and ligand based chimeric antigen receptors strategies using natural ligands and receptors for targeted cell killing |
| topic | chimeric antigen receptor CAR ligand-based CAR natural receptor-based CAR immunotherapy cell therapy |
| url | https://www.mdpi.com/2073-4409/11/1/21 |
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