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Review

Needle in a Haystack: The Naïve Repertoire as a Source of T Cell Receptors for Adoptive Therapy with Engineered T Cells

1
Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), 81675 Munich, Germany
2
German Center for Infection Research (DZIF), Partner Site Munich, 81675 Munich, Germany
3
Focus Group ‘‘Clinical Cell Processing and Purification”, Institute for Advanced Study, Technische Universität München (TUM), 81675 Munich, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(21), 8324; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218324
Received: 29 September 2020 / Revised: 27 October 2020 / Accepted: 2 November 2020 / Published: 6 November 2020
(This article belongs to the Special Issue Recent Advances in T Cell Immunity)
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. View Full-Text
Keywords: adoptive cell therapy; T cell receptor; naïve repertoire; tumor neoantigens adoptive cell therapy; T cell receptor; naïve repertoire; tumor neoantigens
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MDPI and ACS Style

D’Ippolito, E.; Wagner, K.I.; Busch, D.H. Needle in a Haystack: The Naïve Repertoire as a Source of T Cell Receptors for Adoptive Therapy with Engineered T Cells. Int. J. Mol. Sci. 2020, 21, 8324. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218324

AMA Style

D’Ippolito E, Wagner KI, Busch DH. Needle in a Haystack: The Naïve Repertoire as a Source of T Cell Receptors for Adoptive Therapy with Engineered T Cells. International Journal of Molecular Sciences. 2020; 21(21):8324. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218324

Chicago/Turabian Style

D’Ippolito, Elvira, Karolin I. Wagner, and Dirk H. Busch 2020. "Needle in a Haystack: The Naïve Repertoire as a Source of T Cell Receptors for Adoptive Therapy with Engineered T Cells" International Journal of Molecular Sciences 21, no. 21: 8324. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218324

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