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Needle in a Haystack: The Naïve Repertoire as a Source of T Cell Receptors for Adoptive Therapy with Engineered T Cells
T cell engineering with antigen-specific T cell receptors (TCRs) has allowed the generation of increasingly specific, reliable, and versatile T cell products with near-physiological features. However, a broad applicability of TCR-based therapies in cancer is still limited by the restricted number of...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664211/ https://www.ncbi.nlm.nih.gov/pubmed/33171940 http://dx.doi.org/10.3390/ijms21218324 |
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author | D’Ippolito, Elvira Wagner, Karolin I. Busch, Dirk H |
author_facet | D’Ippolito, Elvira Wagner, Karolin I. Busch, Dirk H |
author_sort | D’Ippolito, Elvira |
collection | PubMed |
description | T cell engineering with antigen-specific T cell receptors (TCRs) has allowed the generation of increasingly specific, reliable, and versatile T cell products with near-physiological features. However, a broad applicability of TCR-based therapies in cancer is still limited by the restricted number of TCRs, often also of suboptimal potency, available for clinical use. In addition, targeting of tumor neoantigens with TCR-engineered T cell therapy moves the field towards a highly personalized treatment, as tumor neoantigens derive from somatic mutations and are extremely patient-specific. Therefore, relevant TCRs have to be de novo identified for each patient and within a narrow time window. The naïve repertoire of healthy donors would represent a reliable source due to its huge diverse TCR repertoire, which theoretically entails T cells for any antigen specificity, including tumor neoantigens. As a challenge, antigen-specific naïve T cells are of extremely low frequency and mostly of low functionality, making the identification of highly functional TCRs finding a “needle in a haystack.” In this review, we present the technological advancements achieved in high-throughput mapping of patient-specific neoantigens and corresponding cognate TCRs and how these platforms can be used to interrogate the naïve repertoire for a fast and efficient identification of rare but therapeutically valuable TCRs for personalized adoptive T cell therapy. |
format | Online Article Text |
id | pubmed-7664211 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76642112020-11-14 Needle in a Haystack: The Naïve Repertoire as a Source of T Cell Receptors for Adoptive Therapy with Engineered T Cells D’Ippolito, Elvira Wagner, Karolin I. Busch, Dirk H Int J Mol Sci Review T cell engineering with antigen-specific T cell receptors (TCRs) has allowed the generation of increasingly specific, reliable, and versatile T cell products with near-physiological features. However, a broad applicability of TCR-based therapies in cancer is still limited by the restricted number of TCRs, often also of suboptimal potency, available for clinical use. In addition, targeting of tumor neoantigens with TCR-engineered T cell therapy moves the field towards a highly personalized treatment, as tumor neoantigens derive from somatic mutations and are extremely patient-specific. Therefore, relevant TCRs have to be de novo identified for each patient and within a narrow time window. The naïve repertoire of healthy donors would represent a reliable source due to its huge diverse TCR repertoire, which theoretically entails T cells for any antigen specificity, including tumor neoantigens. As a challenge, antigen-specific naïve T cells are of extremely low frequency and mostly of low functionality, making the identification of highly functional TCRs finding a “needle in a haystack.” In this review, we present the technological advancements achieved in high-throughput mapping of patient-specific neoantigens and corresponding cognate TCRs and how these platforms can be used to interrogate the naïve repertoire for a fast and efficient identification of rare but therapeutically valuable TCRs for personalized adoptive T cell therapy. MDPI 2020-11-06 /pmc/articles/PMC7664211/ /pubmed/33171940 http://dx.doi.org/10.3390/ijms21218324 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review D’Ippolito, Elvira Wagner, Karolin I. Busch, Dirk H Needle in a Haystack: The Naïve Repertoire as a Source of T Cell Receptors for Adoptive Therapy with Engineered T Cells |
title | Needle in a Haystack: The Naïve Repertoire as a Source of T Cell Receptors for Adoptive Therapy with Engineered T Cells |
title_full | Needle in a Haystack: The Naïve Repertoire as a Source of T Cell Receptors for Adoptive Therapy with Engineered T Cells |
title_fullStr | Needle in a Haystack: The Naïve Repertoire as a Source of T Cell Receptors for Adoptive Therapy with Engineered T Cells |
title_full_unstemmed | Needle in a Haystack: The Naïve Repertoire as a Source of T Cell Receptors for Adoptive Therapy with Engineered T Cells |
title_short | Needle in a Haystack: The Naïve Repertoire as a Source of T Cell Receptors for Adoptive Therapy with Engineered T Cells |
title_sort | needle in a haystack: the naïve repertoire as a source of t cell receptors for adoptive therapy with engineered t cells |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664211/ https://www.ncbi.nlm.nih.gov/pubmed/33171940 http://dx.doi.org/10.3390/ijms21218324 |
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