TY - JOUR
T1 - Characterization and modulation of anti-alpha beta TCR antibodies and their respective binding sites at the beta TCR chain to enrich engineered T cells
AU - Kierkels, Guido J J
AU - van Diest, Eline
AU - Hernández-López, Patricia
AU - Scheper, Wouter
AU - de Bruin, Anja C M
AU - Frijlink, Elselien
AU - Aarts-Riemens, Tineke
AU - van Dooremalen, Sanne F J
AU - Beringer, Dennis X
AU - Oostvogels, Rimke
AU - Kramer, Lovro
AU - Straetemans, Trudy
AU - Uckert, Wolfgang
AU - Sebestyén, Zsolt
AU - Kuball, Jürgen
N1 - Publisher Copyright:
© 2021 The Author(s)
PY - 2021/9/10
Y1 - 2021/9/10
N2 - 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.
AB - 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.
U2 - 10.1016/j.omtm.2021.06.011
DO - 10.1016/j.omtm.2021.06.011
M3 - Article
C2 - 34514030
SN - 2329-0501
VL - 22
SP - 388
EP - 400
JO - Molecular Therapy - Methods and Clinical Development
JF - Molecular Therapy - Methods and Clinical Development
ER -