The Intracellular Proteome as a Source for Novel Targets in CAR-T and T-Cell Engagers-Based Immunotherapy
The impressive clinical success of cancer immunotherapy has motivated the continued search for new targets that may serve to guide potent effector functions in an attempt to efficiently kill malignant cells. The intracellular proteome is an interesting source for such new targets, such as neo-antige...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/1/27 |
| _version_ | 1827760900194435072 |
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| author | Inbar Arman Maya Haus-Cohen Yoram Reiter |
| author_facet | Inbar Arman Maya Haus-Cohen Yoram Reiter |
| author_sort | Inbar Arman |
| collection | DOAJ |
| description | The impressive clinical success of cancer immunotherapy has motivated the continued search for new targets that may serve to guide potent effector functions in an attempt to efficiently kill malignant cells. The intracellular proteome is an interesting source for such new targets, such as neo-antigens and others, with growing interest in their application for cell-based immunotherapies. These intracellular-derived targets are peptides presented by MHC class I molecules on the cell surface of malignant cells. These disease-specific class I HLA–peptide complexes can be targeted by specific TCRs or by antibodies that mimic TCR-specificity, termed TCR-like (TCRL) antibodies. Adoptive cell transfer of TCR engineered T cells and T-cell-receptor-like based CAR-T cells, targeted against a peptide-MHC of interest, are currently tested as cancer therapeutic agents in pre-clinical and clinical trials, along with soluble TCR- and TCRL-based agents, such as immunotoxins and bi-specific T cell engagers. Targeting the intracellular proteome using TCRL- and TCR-based molecules shows promising results in cancer immunotherapy, as exemplified by the success of the anti-gp100/HLA-A2 TCR-based T cell engager, recently approved by the FDA for the treatment of unresectable or metastatic uveal melanoma. This review is focused on the selection and isolation processes of TCR- and TCRL-based targeting moieties, with a spotlight on pre-clinical and clinical studies, examining peptide-MHC targeting agents in cancer immunotherapy. |
| first_indexed | 2024-03-11T10:05:41Z |
| format | Article |
| id | doaj.art-37e2875d544446979d6c0b71614ee3ea |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T10:05:41Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-37e2875d544446979d6c0b71614ee3ea2023-11-16T15:05:05ZengMDPI AGCells2073-44092022-12-011212710.3390/cells12010027The Intracellular Proteome as a Source for Novel Targets in CAR-T and T-Cell Engagers-Based ImmunotherapyInbar Arman0Maya Haus-Cohen1Yoram Reiter2Laboratory of Molecular Immunology and Immunotherapy, Faculty of Biology, Technion–Israel Institute of Haifa, Haifa 320003, IsraelLaboratory of Molecular Immunology and Immunotherapy, Faculty of Biology, Technion–Israel Institute of Haifa, Haifa 320003, IsraelLaboratory of Molecular Immunology and Immunotherapy, Faculty of Biology, Technion–Israel Institute of Haifa, Haifa 320003, IsraelThe impressive clinical success of cancer immunotherapy has motivated the continued search for new targets that may serve to guide potent effector functions in an attempt to efficiently kill malignant cells. The intracellular proteome is an interesting source for such new targets, such as neo-antigens and others, with growing interest in their application for cell-based immunotherapies. These intracellular-derived targets are peptides presented by MHC class I molecules on the cell surface of malignant cells. These disease-specific class I HLA–peptide complexes can be targeted by specific TCRs or by antibodies that mimic TCR-specificity, termed TCR-like (TCRL) antibodies. Adoptive cell transfer of TCR engineered T cells and T-cell-receptor-like based CAR-T cells, targeted against a peptide-MHC of interest, are currently tested as cancer therapeutic agents in pre-clinical and clinical trials, along with soluble TCR- and TCRL-based agents, such as immunotoxins and bi-specific T cell engagers. Targeting the intracellular proteome using TCRL- and TCR-based molecules shows promising results in cancer immunotherapy, as exemplified by the success of the anti-gp100/HLA-A2 TCR-based T cell engager, recently approved by the FDA for the treatment of unresectable or metastatic uveal melanoma. This review is focused on the selection and isolation processes of TCR- and TCRL-based targeting moieties, with a spotlight on pre-clinical and clinical studies, examining peptide-MHC targeting agents in cancer immunotherapy.https://www.mdpi.com/2073-4409/12/1/27T-cell-receptor-like antibodiesT cell receptor mimicchimeric antigen receptorpeptideMHC |
| spellingShingle | Inbar Arman Maya Haus-Cohen Yoram Reiter The Intracellular Proteome as a Source for Novel Targets in CAR-T and T-Cell Engagers-Based Immunotherapy Cells T-cell-receptor-like antibodies T cell receptor mimic chimeric antigen receptor peptide MHC |
| title | The Intracellular Proteome as a Source for Novel Targets in CAR-T and T-Cell Engagers-Based Immunotherapy |
| title_full | The Intracellular Proteome as a Source for Novel Targets in CAR-T and T-Cell Engagers-Based Immunotherapy |
| title_fullStr | The Intracellular Proteome as a Source for Novel Targets in CAR-T and T-Cell Engagers-Based Immunotherapy |
| title_full_unstemmed | The Intracellular Proteome as a Source for Novel Targets in CAR-T and T-Cell Engagers-Based Immunotherapy |
| title_short | The Intracellular Proteome as a Source for Novel Targets in CAR-T and T-Cell Engagers-Based Immunotherapy |
| title_sort | intracellular proteome as a source for novel targets in car t and t cell engagers based immunotherapy |
| topic | T-cell-receptor-like antibodies T cell receptor mimic chimeric antigen receptor peptide MHC |
| url | https://www.mdpi.com/2073-4409/12/1/27 |
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