Structure-guided engineering of immunotherapies targeting TRBC1 and TRBC2 in T cell malignancies
In: Nature Communications, Jg. 15 (2024), Heft 1, S. 1-16
Online
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Zugriff:
Abstract Peripheral T cell lymphomas are typically aggressive with a poor prognosis. Unlike other hematologic malignancies, the lack of target antigens to discriminate healthy from malignant cells limits the efficacy of immunotherapeutic approaches. The T cell receptor expresses one of two highly homologous chains [T cell receptor β-chain constant (TRBC) domains 1 and 2] in a mutually exclusive manner, making it a promising target. Here we demonstrate specificity redirection by rational design using structure-guided computational biology to generate a TRBC2-specific antibody (KFN), complementing the antibody previously described by our laboratory with unique TRBC1 specificity (Jovi-1) in targeting broader spectrum of T cell malignancies clonally expressing either of the two chains. This permits generation of paired reagents (chimeric antigen receptor-T cells) specific for TRBC1 and TRBC2, with preclinical evidence to support their efficacy in T cell malignancies.
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Structure-guided engineering of immunotherapies targeting TRBC1 and TRBC2 in T cell malignancies
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Autor/in / Beteiligte Person: | Ferrari, Mathieu ; Righi, Matteo ; Baldan, Vania ; Wawrzyniecka, Patrycja ; Bulek, Anna ; Kinna, Alexander ; Ma, Biao ; Bughda, Reyisa ; Akbar, Zulaikha ; Srivastava, Saket ; Gannon, Isaac ; Robson, Mathew ; Sillibourne, James ; Jha, Ram ; El-Kholy, Mohamed ; Oliver Muhammad Amin ; Kokalaki, Evangelia ; Mohammed Amin Banani ; Hussain, Rehan ; Day, William ; Wen Chean Lim ; Ghongane, Priyanka ; Hopkins, Jade R. ; Jungherz, Dennis ; Herling, Marco ; Welin, Martin ; Surade, Sachin ; Dyson, Michael ; McCafferty, John ; Logan, Derek ; Cordoba, Shaun ; Thomas, Simon ; Sewell, Andrew ; Maciocia, Paul ; Onuoha, Shimobi ; Pule, Martin |
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Zeitschrift: | Nature Communications, Jg. 15 (2024), Heft 1, S. 1-16 |
Veröffentlichung: | Nature Portfolio, 2024 |
Medientyp: | academicJournal |
ISSN: | 2041-1723 (print) |
DOI: | 10.1038/s41467-024-45854-3 |
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