Characterization and modulation of anti-alpha beta TCR antibodies and their respective binding sites at the beta TCR chain to enrich engineered T cells

Guido J J Kierkels, Eline van Diest, Patricia Hernández-López, Wouter Scheper, Anja C M de Bruin, Elselien Frijlink, Tineke Aarts-Riemens, Sanne F J van Dooremalen, Dennis X Beringer, Rimke Oostvogels, Lovro Kramer, Trudy Straetemans, Wolfgang Uckert, Zsolt Sebestyén, Jürgen Kuball

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Abstract

T cell engineering strategies offer cures to patients and have entered clinical practice with chimeric antibody-based receptors; αβT cell receptor (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 increased efficacy, reduced potential side effects, and improved safety of newly to-be-tested lead structures. By characterizing the antigen-binding interface of a good manufacturing process (GMP)-grade anti-αβTCR antibody, usually used for depletion of αβT cells from stem cell transplantation products, we developed a strategy that allows for the purification of untouched αβTCR-engineered immune cells by changing 2 amino acids only in the TCRβ chain constant domain of introduced TCR chains. Alternatively, we engineered an antibody that targets an extended mutated interface of 9 amino acids in the TCRβ chain constant domain and provides the opportunity to further develop depletion strategies of engineered immune cells.

Original languageEnglish
Pages (from-to)388-400
Number of pages13
JournalMolecular Therapy - Methods and Clinical Development
Volume22
DOIs
Publication statusPublished - 10 Sept 2021

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