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Characterization and modulation of anti- αβTCR antibodies and their respective binding sites at the βTCR chain to enrich engineered T cells

Authors

  • G.J.J. Kierkels
  • E. van Diest
  • P. Hernández-López
  • W. Scheper
  • A.C.M. de Bruin
  • E. Frijlink
  • T. Aarts-Riemens
  • S.F.J. van Dooremalen
  • D.X. Beringer
  • R. Oostvogels
  • L. Kramer
  • T. Straetemans
  • W. Uckert
  • Z. Sebestyén
  • J. Kuball

Journal

  • Molecular Therapy - Methods and Clinical Development

Citation

  • Mol Ther Methods Clin Dev 22 (10): 388-400

Abstract

  • T cell engineering strategies offer cure to patients and entered clinical practice with chimeric antibody-based receptors, αβT cell receptors (αβTCR)-based strategies are however lagging behind. To allow a more rapid and successful translation to successful concepts also using αβTCRs for engineering, incorporating a method for the purification of genetically modified T cells, as well as engineered T cell deletion after transfer into patients, could be beneficial. This would allow to increase efficacy, reduce potential side effects, and improve safety of newly, to be tested, lead structures. By characterizing the antigen binding interface of a GMP-grade anti-αβTCR antibody, usually used for depletion of αβT cells from stem cell transplantation products, we developed a strategy which allows for the purification of untouched αβTCR engineered immune cells by changing two amino acids only in the TCR β chain constant domain of introduced TCR chains. Vice versa, we engineered an antibody, which targets an extended mutated interface of nine amino acids in the TCR β chain constant domain, and provides the opportunity to further develop depletion strategies of engineered immune cells.


DOI

doi:10.1016/j.omtm.2021.06.011