TY - JOUR
T1 - Minimally manipulated murine regulatory T cells purified by reversible Fab Multimers are potent suppressors for adoptive T-cell therapy
AU - Mohr, Fabian
AU - Fischer, Julius Clemens
AU - Nikolaus, Marc
AU - Stemberger, Christian
AU - Dreher, Stefan
AU - Verschoor, Admar
AU - Haas, Tobias
AU - Poeck, Hendrik
AU - Busch, Dirk H.
N1 - Publisher Copyright:
© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2017/12
Y1 - 2017/12
N2 - The transfer of regulatory T cells, either freshly isolated, or modified, represents a promising therapeutic approach to dampen misdirected immune responses, like autoimmune diseases, chronic inflammatory syndromes and graft versus host disease. Clinical isolation of highly pure regulatory T cell (Treg) populations is still challenging and labeling reagents can influence their viability and functionality, potentially altering the potency of isolated Treg cell products. Here we show that reversible Fab multimer-based Treg purification can prevent conventional antibody label-induced interferences in vitro and in vivo. Remaining isolation reagents negatively interfere with Treg engraftment efficacy in C57BL/6 wild-type mice due to Fcγ-receptor- as well as IL-2 receptor-mediated mechanisms. Using a preclinical model for acute GvHD, we further show that purified ‘label-freed’ Tregs are protective at substantially lower cell numbers as compared to conventional nonreversible antibody staining, translating into significantly improved survival of mice treated with minimally manipulated Tregs. These findings have important clinical relevance for future Treg-based cell therapies.
AB - The transfer of regulatory T cells, either freshly isolated, or modified, represents a promising therapeutic approach to dampen misdirected immune responses, like autoimmune diseases, chronic inflammatory syndromes and graft versus host disease. Clinical isolation of highly pure regulatory T cell (Treg) populations is still challenging and labeling reagents can influence their viability and functionality, potentially altering the potency of isolated Treg cell products. Here we show that reversible Fab multimer-based Treg purification can prevent conventional antibody label-induced interferences in vitro and in vivo. Remaining isolation reagents negatively interfere with Treg engraftment efficacy in C57BL/6 wild-type mice due to Fcγ-receptor- as well as IL-2 receptor-mediated mechanisms. Using a preclinical model for acute GvHD, we further show that purified ‘label-freed’ Tregs are protective at substantially lower cell numbers as compared to conventional nonreversible antibody staining, translating into significantly improved survival of mice treated with minimally manipulated Tregs. These findings have important clinical relevance for future Treg-based cell therapies.
UR - http://www.scopus.com/inward/record.url?scp=85029410286&partnerID=8YFLogxK
U2 - 10.1002/eji.201747137
DO - 10.1002/eji.201747137
M3 - Journal articles
C2 - 28833039
AN - SCOPUS:85029410286
SN - 0014-2980
VL - 47
SP - 2153
EP - 2162
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 12
ER -