Minimally manipulated murine regulatory T cells purified by reversible Fab Multimers are potent suppressors for adoptive T-cell therapy

Fabian Mohr, Julius Clemens Fischer, Marc Nikolaus, Christian Stemberger, Stefan Dreher, Admar Verschoor, Tobias Haas, Hendrik Poeck, Dirk H. Busch*

*Corresponding author for this work
7 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalEuropean Journal of Immunology
Volume47
Issue number12
Pages (from-to)2153-2162
Number of pages10
ISSN0014-2980
DOIs
Publication statusPublished - 12.2017

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)

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