title: Retargeting of human regulatory T cells by single-chain bispecific antibodies.
abstract: Bispecific Abs hold great potential for immunotherapy of malignant diseases. Because the first components of this new drug class are now entering clinical trials, all aspects of their mode of action should be well understood. Several studies proved that CD8(+) and CD4(+) effector T cells can be successfully redirected and activated against tumor cells by bispecific Abs both in vitro and in vivo. To our knowledge, this study provides the first evidence that bispecific Abs can also redirect and activate regulatory T cells against a surface Ag, independently of their TCR specificity. After cross-linking, via a bispecific Ab, redirected regulatory T cells upregulate the activation markers CD69 and CD25, as well as regulatory T cell-associated markers, like CTLA-4 and FOXP3. The activated regulatory T cells secrete the immunosuppressive cytokine IL-10, but, in contrast to CD8(+) and CD4(+) effector T cells, almost no inflammatory cytokines. In addition, the redirected regulatory T cells are able to suppress effector functions of activated autologous CD4(+) T cells both in vitro and in vivo. Therefore, the potential risk for activation of regulatory T cells should be taken into consideration when bispecific Abs are applied for the treatment of malignant diseases. In contrast, an Ag/tissue-specific redirection of regulatory T cells with bispecific Abs holds great potential for the treatment of autoimmune diseases and graft rejection.
authors.affiliation: Institute of Immunology, Medical Faculty, Carl Gustav Carus Technical University Dresden, 01307 Dresden, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Koristka
authors.forename: Marc
authors.initials: M
authors.lastname: Cartellieri
authors.forename: Anke
authors.initials: A
authors.lastname: Theil
authors.forename: Anja
authors.initials: A
authors.lastname: Feldmann
authors.forename: Claudia
authors.initials: C
authors.lastname: Arndt
authors.forename: Slava
authors.initials: S
authors.lastname: Stamova
authors.forename: Irene
authors.initials: I
authors.lastname: Michalk
authors.forename: Katrin
authors.initials: K
authors.lastname: Töpfer
authors.forename: Achim
authors.initials: A
authors.lastname: Temme
authors.forename: Karsten
authors.initials: K
authors.lastname: Kretschmer
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.forename: Marc
authors.initials: M
authors.lastname: Schmitz
authors.forename: Michael
authors.initials: M
authors.lastname: Bachmann
mesh_terms: D018033:Antibodies, Bispecific / Q000494:pharmacology / Q000627:therapeutic use*; D000954:Antigens, Surface / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D016753:Interleukin-10; D008213:Lymphocyte Activation; D058990:Molecular Targeted Therapy / Q000379:methods*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*
chemical_list: D018033:Antibodies, Bispecific; D000954:Antigens, Surface; D016753:Interleukin-10