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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1520103

Development of a recombinant human IgG1 monoclonal antibody against the TRBV5-1 segment of the T cell receptor for the treatment of mature T cell neoplasms

Provisionally accepted
Michele Pitaro Michele Pitaro 1*Giovanni Antonini Giovanni Antonini 2Alessandro Arcovito Alessandro Arcovito 3Francesco Buccisano Francesco Buccisano 4Alfredo De Lauro Alfredo De Lauro 2Maria Irno Consalvo Maria Irno Consalvo 4Valentina Gallo Valentina Gallo 2Noah Giacon Noah Giacon 5Giuseppe Felice Mangiatordi Giuseppe Felice Mangiatordi 6Maddalena Pacelli Maddalena Pacelli 1Maria Teresa Pitaro Maria Teresa Pitaro 7Fabio Polticelli Fabio Polticelli 2Matteo Sorrenti Matteo Sorrenti 7Adriano Venditti Adriano Venditti 4
  • 1 Istituto Nazionale Biostrutture e Biosistemi, Rome, Italy
  • 2 Dipartimento di Scienze, Università di Roma Tre, Rome, Italy
  • 3 Agostino Gemelli University Polyclinic (IRCCS), Rome, Lazio, Italy
  • 4 Policlinico Tor Vergata, Rome, Lazio, Italy
  • 5 Dipartimento di Scienze Biotecnologiche di Base, Cliniche, Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore,, Rome, Italy
  • 6 Istituto di Cristallografia, Consiglio Nazionale delle Ricerche, Bari, Italy
  • 7 Tiber Biotech Srl, Rome, Italy

The final, formatted version of the article will be published soon.

    Background: Mature T-cell neoplasms arise from the neoplastic transformation of a single T lymphocyte, and all cells in a neoplastic clone share the same V segment in the beta chain of the T-cell receptor (TCR). These segments may represent an innovative target for the development of targeted therapies.A specific V segment of the TCR beta chain (TRBV5-1) was analyzed using bioinformatic tools, identifying three potential antigenic peptides. One of these peptides, selected for synthesis, was used to screen a library of human single-chain variable fragments through phage display. One fragment demonstrated high affinity and specificity for the antigen and was used to produce a human monoclonal antibody of the IgG1 class.Results: Surface plasmon resonance studies confirmed the high affinity of the monoclonal antibody for the antigen in the nanomolar range. Flow cytometry analysis on patients samples demonstrated that the antibody, conjugated with a fluorochrome, selectively binds t o tumor T lymphocytes expressing TRBV5-1, without binding to other lymphocytes or blood cell components.The development of fully human IgG1 monoclonal antibodies targeting specific V segments of the TCR beta chain represents a potential therapeutic option for patients with mature T-cell neoplasms.

    Keywords: T cell neoplasms, T-cell receptor (TCR), human IgG1 monoclonal antibodies, phage display, Surface Plasmon Resonance, Flow Cytometry, Antigenic peptides

    Received: 30 Oct 2024; Accepted: 21 Nov 2024.

    Copyright: © 2024 Pitaro, Antonini, Arcovito, Buccisano, De Lauro, Irno Consalvo, Gallo, Giacon, Mangiatordi, Pacelli, Pitaro, Polticelli, Sorrenti and Venditti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Michele Pitaro, Istituto Nazionale Biostrutture e Biosistemi, Rome, Italy

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.