Anti-CD4 therapy of acute rejection in long-term renal allograft recipients

Reinke, Petra; Miller, Hannah; Fietze, Ellen; Herberger, D; Volk, Hans‐Dieter; Neuhaus, Kathrin; Herberger, J.; Baehr, R.; Emmrich, Frank

doi:10.1016/0140-6736(91)91285-3

Cited by 24 publications

(8 citation statements)

References 4 publications

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“…The other selected PDPs demonstrated no or extremely low blocking of IL2 secretion. Taken together, these results indicate that, as already demonstrated for other anti‐CD4 mAbs [52,53], the CDR‐H1‐derived PDP CB1 is able to inhibit the antigen‐presenting function, a biological property also demonstrated for the 13B8.2 parental mAb.…”

Section: Resultssupporting

confidence: 81%

“…In this study, we demonstrated that the CDR‐H1‐derived PDP CB1 displays significant and specific biological properties mimicking those of the parental anti‐CD4 13B8.2 mAb. Firstly, in an in vitro model of MHC class II‐restricted immune response, we demonstrated that anti‐CD4 PDP CB1, as well as parental mAb 13B8.2, inhibits IL2 secretion by activated T cells following antigen presentation; this inhibitory effect, classically observed for anti‐CD4 mAbs [52,53], was dose‐dependent. Since, anti‐CD4 mAbs have been described to prevent T cells from IL2‐induced proliferation and B cell adhesion through inhibition of Ca 2+ and p21 ras signaling pathways [57,58], it remains to be assessed whether our anti‐CD4 PDPs could interfere with such mechanisms.…”

Section: Discussionmentioning

confidence: 82%

See 1 more Smart Citation

Efficient CD4 binding and immunosuppressive properties of the 13B8.2 monoclonal antibody are displayed by its CDR‐H1‐derived peptide CB1¹

Bès

Briant-Longuet

Cerruti³

et al. 2001

FEBS Letters

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A systematic exploration of the V H 2/V U 12^13 variable domains of the anti-CD4 monoclonal antibody (mAb) 13B8.2 was performed by the Spot method to screen for paratope-derived peptides (PDPs) demonstrating CD4 binding ability. Nine peptides, named CB1 to CB9, were identified, synthesized in a cyclic and soluble form and tested for binding to recombinant soluble CD4. Among them, CB1, CB2 and CB8 showed high anti-CD4 activity. Competition studies for CD4 binding indicated that PDPs CB1, CB8, and the parental mAb 13B8.2 recognized the same complementarity determining region (CDR)3-like loop region. PDP CB1 was shown to mimic the biological properties of 13B8.2 mAb in two independent cellular assays, demonstrating inhibitory activities in the micromolar range on antigen presentation and human immunodeficiency virus promoter activation. Our results indicate that the bioactive CDR-H1 PDP CB1 has retained a significant part of the parental 13B8.2 mAb properties and might be a lead for the design of anti-CD4 peptidomimetics of clinical interest. ß

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Section: Resultssupporting

confidence: 81%

Section: Discussionmentioning

confidence: 82%

Efficient CD4 binding and immunosuppressive properties of the 13B8.2 monoclonal antibody are displayed by its CDR‐H1‐derived peptide CB1¹

Bès

Briant-Longuet

Cerruti³

et al. 2001

FEBS Letters

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“…Much effort has been devoted to the dissection of the individual roles played by CD4 + and CD8 + T cells in GVHD (reviewed in [8]). The murine anti-human CD4 monoclonal antibody (mAb) MAX.16H5 IgG 1 has been used to modulate CD4 + T-cell function in patients with autoimmune diseases [11] or as a protective therapy against transplant rejection (TABLE 1) [12]. The epitope-specific ex vivo modulation of an allogeneic HSCT by the anti-human CD4 antibody MAX.16H5 IgG 1 simultaneously enhances GVL and suppresses GVHD [13].…”

Section: Cellular Targets In Gvhdmentioning

confidence: 99%

Recent advances on cellular therapies and immune modulators for graft-versus-host disease

Filippini

Rutella

2014

Expert Review of Clinical Immunology

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The efficacy of allogeneic hematopoietic stem cell transplantation is counterbalanced by the occurrence of life-threatening immune-mediated complications, such as graft-versus-host disease (GVHD), a multistep disease which is reportedly fatal to approximately 15% of transplant recipients. It is now established that T-cell-dendritic cell interactions, T-cell activation, release of proinflammatory cytokines and T-cell trafficking partake in GVHD pathogenesis. This article will focus on the most recent strategies aimed at preventing/treating GVHD by manipulating components of the innate and adaptive immune response from both the donor and the host.

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“…Patients suffering from severe acute rejection after kidney transplantation also benefitted from the therapy with MAX.16H5 IgG 1 (22). Histological signs of acute rejection (if present) disappeared as a response to the MAX.16H5 IgG 1 treatment.…”

Section: Max16h5 Igg1 In the Treatment Of Autoimmune Diseasesmentioning

confidence: 99%

The Epitope-Specific Anti-human CD4 Antibody MAX.16H5 and Its Role in Immune Tolerance

et al. 2019

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T cell modulation in the clinical background of autoimmune diseases or allogeneic cell and organ transplantations with concurrent preservation of their natural immunological functions (e.g., pathogen defense) is the major obstacle in immunology. An anti-human CD4 antibody (MAX.16H5) was applied intravenously in clinical trials for the treatment of autoimmune diseases (e.g., rheumatoid arthritis) and acute late-onset rejection after transplantation of a renal allograft. The response rates were remarkable and no critical allergic problems or side effects were obtained. During the treatment of autoimmune diseases with the murine MAX.16H5 IgG 1 antibody its effector mechanisms with effects on lymphocytes, cytokines, laboratory and clinical parameters, adverse effects as well as pharmacodynamics and kinetics were studied in detail. However, as the possibility of developing immune reactions against the murine IgG 1 Fc-part remains, the murine antibody was chimerized, inheriting CD4-directed variable domains of the MAX.16H5 IgG 1 connected to a human IgG 4 backbone. Both antibodies were studied in vitro and in specific humanized mouse transplantation models in vivo with a new scope. By ex vivo incubation of an allogeneic immune cell transplant with MAX.16H5 a new therapy strategy has emerged for the first time enabling both the preservation of the graft-vs.-leukemia (GVL) effect and the permanent suppression of the acute graft-vs.-host disease (aGVHD) without conventional immunosuppression. In this review, we especially focus on experimental data and clinical trials obtained from the treatment of autoimmune diseases with the murine MAX.16H5 IgG 1 antibody. Insights gained from these trials have paved the way to better understand the effects with the chimerized MAX.16H5 IgG 4 as novel therapeutic approach in the context of GVHD prevention.

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Anti-CD4 therapy of acute rejection in long-term renal allograft recipients

Cited by 24 publications

References 4 publications

Efficient CD4 binding and immunosuppressive properties of the 13B8.2 monoclonal antibody are displayed by its CDR‐H1‐derived peptide CB1¹

Efficient CD4 binding and immunosuppressive properties of the 13B8.2 monoclonal antibody are displayed by its CDR‐H1‐derived peptide CB1¹

Recent advances on cellular therapies and immune modulators for graft-versus-host disease

The Epitope-Specific Anti-human CD4 Antibody MAX.16H5 and Its Role in Immune Tolerance

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Anti-CD4 therapy of acute rejection in long-term renal allograft recipients

Cited by 24 publications

References 4 publications

Efficient CD4 binding and immunosuppressive properties of the 13B8.2 monoclonal antibody are displayed by its CDR‐H1‐derived peptide CB11

Efficient CD4 binding and immunosuppressive properties of the 13B8.2 monoclonal antibody are displayed by its CDR‐H1‐derived peptide CB11

Recent advances on cellular therapies and immune modulators for graft-versus-host disease

The Epitope-Specific Anti-human CD4 Antibody MAX.16H5 and Its Role in Immune Tolerance

Contact Info

Product

Resources

About

Efficient CD4 binding and immunosuppressive properties of the 13B8.2 monoclonal antibody are displayed by its CDR‐H1‐derived peptide CB1¹

Efficient CD4 binding and immunosuppressive properties of the 13B8.2 monoclonal antibody are displayed by its CDR‐H1‐derived peptide CB1¹