Fricke, StephanStephanFrickeHilger, NadjaNadjaHilgerFricke, ChristianChristianFrickeSchönfelder, U.U.SchönfelderBehre, GerhardGerhardBehreRuschpler, PeterPeterRuschplerBoldt, AndreasAndreasBoldtOelkrug, ChristopherChristopherOelkrugSack, UlrichUlrichSackEmmrich, FrankFrankEmmrich2022-03-042022-03-042014https://publica.fraunhofer.de/handle/publica/23554610.1007/s00018-013-1476-02-s2.0-84901679724This is the first report showing that an epitope-specific ex vivo modulation of an allogeneic hematopoietic stem cell graft by the anti-human CD4 antibody MAX.16H5 IgG1 simultaneously facilitates the anti-tumor capacity of the graft (Graft-versus-leukemia effect, GvL) and the long-term suppression of the deleterious side effect Graft-versus-host-disease (GvHD). To distinguish and consolidate GvL from GvHD, the anti-human CD4 antibody MAX16.H5 IgG1 was tested in murine GvHD and tumor models. The survival rate was significantly increased in recipients receiving a MAX.16H5 IgG1 short-term (2 h) pre-incubated graft even when tumor cells were co-transplanted or when recipient mice were treated by MAX.16H5 IgG1 before transplantation. After engraftment, regulatory T-cells are generated only supporting the GvL effect. It was also possible to transfer the immune tolerance from GvHD-free recipient chimeras into third party recipient mice without the need of reapplication of MAX.16H5 IgG1 anti-human CD4 antibodies. These findings are also benefical for patients with leukemia when no matched related or unrelated donor is available and provides a safer allogeneic HSCT, which is more effective against leukemia. It also facilitates allogeneic (stem) cell transplantations for other indications (e.g., autoimmune-disorders).enGvHDGvLallogeneic hematopoetic stem cell transplantationtriple transgenic mouseanti-CD4 antibodies610620journal article