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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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Detalles Bibliográficos
Autores principales: Arman, Inbar, Haus-Cohen, Maya, Reiter, Yoram
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818436/
https://www.ncbi.nlm.nih.gov/pubmed/36611821
http://dx.doi.org/10.3390/cells12010027
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author Arman, Inbar
Haus-Cohen, Maya
Reiter, Yoram
author_facet Arman, Inbar
Haus-Cohen, Maya
Reiter, Yoram
author_sort Arman, Inbar
collection PubMed
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.
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spelling pubmed-98184362023-01-07 The Intracellular Proteome as a Source for Novel Targets in CAR-T and T-Cell Engagers-Based Immunotherapy Arman, Inbar Haus-Cohen, Maya Reiter, Yoram Cells Review 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. MDPI 2022-12-21 /pmc/articles/PMC9818436/ /pubmed/36611821 http://dx.doi.org/10.3390/cells12010027 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Arman, Inbar
Haus-Cohen, Maya
Reiter, Yoram
The Intracellular Proteome as a Source for Novel Targets in CAR-T and T-Cell Engagers-Based Immunotherapy
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 Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818436/
https://www.ncbi.nlm.nih.gov/pubmed/36611821
http://dx.doi.org/10.3390/cells12010027
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