IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-45854-3.html
   My bibliography  Save this article

Structure-guided engineering of immunotherapies targeting TRBC1 and TRBC2 in T cell malignancies

Author

Listed:
  • Mathieu Ferrari

    (Autolus Therapeutics)

  • Matteo Righi

    (Autolus Therapeutics)

  • Vania Baldan

    (Autolus Therapeutics)

  • Patrycja Wawrzyniecka

    (Cardiff University School of Medicine; Heath Park)

  • Anna Bulek

    (Autolus Therapeutics)

  • Alexander Kinna

    (Autolus Therapeutics)

  • Biao Ma

    (Autolus Therapeutics)

  • Reyisa Bughda

    (Autolus Therapeutics)

  • Zulaikha Akbar

    (Autolus Therapeutics)

  • Saket Srivastava

    (Autolus Therapeutics)

  • Isaac Gannon

    (Autolus Therapeutics)

  • Mathew Robson

    (Autolus Therapeutics)

  • James Sillibourne

    (Autolus Therapeutics)

  • Ram Jha

    (Autolus Therapeutics)

  • Mohamed El-Kholy

    (Autolus Therapeutics)

  • Oliver Muhammad Amin

    (Autolus Therapeutics)

  • Evangelia Kokalaki

    (Autolus Therapeutics)

  • Mohammed Amin Banani

    (Autolus Therapeutics)

  • Rehan Hussain

    (Autolus Therapeutics)

  • William Day

    (Autolus Therapeutics)

  • Wen Chean Lim

    (Autolus Therapeutics)

  • Priyanka Ghongane

    (Autolus Therapeutics)

  • Jade R. Hopkins

    (Cardiff University School of Medicine; Heath Park)

  • Dennis Jungherz

    (University of Leipzig Medical Centre)

  • Marco Herling

    (University of Leipzig Medical Centre)

  • Martin Welin

    (Saromics Inc.)

  • Sachin Surade

    (Iontas Ltd., Pampisford)

  • Michael Dyson

    (Iontas Ltd., Pampisford)

  • John McCafferty

    (Iontas Ltd., Pampisford)

  • Derek Logan

    (Saromics Inc.)

  • Shaun Cordoba

    (Autolus Therapeutics)

  • Simon Thomas

    (Autolus Therapeutics)

  • Andrew Sewell

    (Cardiff University School of Medicine; Heath Park)

  • Paul Maciocia

    (Cancer Institute; University College London)

  • Shimobi Onuoha

    (Autolus Therapeutics)

  • Martin Pule

    (Autolus Therapeutics
    Cancer Institute; University College London)

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.

Suggested Citation

  • Mathieu Ferrari & Matteo Righi & Vania Baldan & Patrycja Wawrzyniecka & Anna Bulek & Alexander Kinna & Biao Ma & Reyisa Bughda & Zulaikha Akbar & Saket Srivastava & Isaac Gannon & Mathew Robson & Jame, 2024. "Structure-guided engineering of immunotherapies targeting TRBC1 and TRBC2 in T cell malignancies," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45854-3
    DOI: 10.1038/s41467-024-45854-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-45854-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-45854-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. De Dong & Lvqin Zheng & Jianquan Lin & Bailing Zhang & Yuwei Zhu & Ningning Li & Shuangyu Xie & Yuhang Wang & Ning Gao & Zhiwei Huang, 2019. "Structural basis of assembly of the human T cell receptor–CD3 complex," Nature, Nature, vol. 573(7775), pages 546-552, September.
    2. Hege Beard & Anuradha Cholleti & David Pearlman & Woody Sherman & Kathryn A Loving, 2013. "Applying Physics-Based Scoring to Calculate Free Energies of Binding for Single Amino Acid Mutations in Protein-Protein Complexes," PLOS ONE, Public Library of Science, vol. 8(12), pages 1-1, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Hyun-Kyu Choi & Peiwen Cong & Chenghao Ge & Aswin Natarajan & Baoyu Liu & Yong Zhang & Kaitao Li & Muaz Nik Rushdi & Wei Chen & Jizhong Lou & Michelle Krogsgaard & Cheng Zhu, 2023. "Catch bond models may explain how force amplifies TCR signaling and antigen discrimination," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Marharyta Petukh & Minghui Li & Emil Alexov, 2015. "Predicting Binding Free Energy Change Caused by Point Mutations with Knowledge-Modified MM/PBSA Method," PLOS Computational Biology, Public Library of Science, vol. 11(7), pages 1-23, July.
    3. Kei Saotome & Drew Dudgeon & Kiersten Colotti & Michael J. Moore & Jennifer Jones & Yi Zhou & Ashique Rafique & George D. Yancopoulos & Andrew J. Murphy & John C. Lin & William C. Olson & Matthew C. F, 2023. "Structural analysis of cancer-relevant TCR-CD3 and peptide-MHC complexes by cryoEM," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    4. Kenneth N McGuinness & Weilan Pan & Robert P Sheridan & Grant Murphy & Alejandro Crespo, 2018. "Role of simple descriptors and applicability domain in predicting change in protein thermostability," PLOS ONE, Public Library of Science, vol. 13(9), pages 1-25, September.
    5. Nishant K. Singh & Jesus A. Alonso & Jason R. Devlin & Grant L. J. Keller & George I. Gray & Adarsh K. Chiranjivi & Sara G. Foote & Lauren M. Landau & Alyssa G. Arbuiso & Laura I. Weiss & Aaron M. Ros, 2022. "A class-mismatched TCR bypasses MHC restriction via an unorthodox but fully functional binding geometry," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    6. Muaz Nik Rushdi & Victor Pan & Kaitao Li & Hyun-Kyu Choi & Stefano Travaglino & Jinsung Hong & Fletcher Griffitts & Pragati Agnihotri & Roy A. Mariuzza & Yonggang Ke & Cheng Zhu, 2022. "Cooperative binding of T cell receptor and CD4 to peptide-MHC enhances antigen sensitivity," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45854-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.