IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation

Jordan, Stanley C.; Lorant, Tomas; Choi, Jua; Kjellman, Christian; Winstedt, Lena; Bengtsson, Mats; Zhang, Xiaohai; Eich, Torsten; Toyoda, Mieko; Eriksson, Britt‐Marie; Ge, Shili; Peng, Alice; Järnum, Sofia; Wood, Kathryn J.; Lundgren, Torbjörn; Wennberg, Lars; Bäckman, Lars; Larsson, Erik; Villicana, Rafael; Kahwaji, Joseph; Louie, Sabrina; Kang, Alexis; Haas, Mark; Nast, Cynthia C.; Vo, Ashley; Tufveson, Gunnar

doi:10.1056/nejmoa1612567

Cited by 280 publications

(228 citation statements)

References 29 publications

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“…48 In addition, a Streptococcus pyogenes –derived endopeptidase that degrades immunoglobulin G (IgG), thereby inhibiting complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity, was shown to reduce or eliminate DSAs, permitting HLA-incompatible renal transplantation in 24 of 25 patients. 49 These novel agents may soon contribute to the prevention/treatment of AMR in heart recipients.…”

Section: Immunosuppression: Advances and The Lack Thereofmentioning

confidence: 99%

Advances in the immunology of heart transplantation

Madsen

2017

The Journal of Heart and Lung Transplantation

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Section: Immunosuppression: Advances and The Lack Thereofmentioning

confidence: 99%

Advances in the immunology of heart transplantation

Madsen

2017

The Journal of Heart and Lung Transplantation

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“…The paper published in the New England Journal of Medicine describing the use of IgG endopeptidase for desensitization in kidney transplantation by Jordan et al (8) reported results from two separate phase 1-2 studies conducted in the United States and Sweden. The primary objective was to examine safety, and secondarily, it examined efficacy of IgG endopeptidase.…”

mentioning

confidence: 99%

Immunoglobulin G–Degrading Enzyme of Streptococcus pyogenes (IdeS), Desensitization, and the Kidney Allocation System

Huang

Jordan

2018

CJASN

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“…2013-005417-13) in kidney transplantation patients. Furthermore, IdeS is currently being investigated in two ongoing phase II studies, both in kidney transplantation patients (45). Data on IdeS pharmacokinetics and pharmacodynamics profile have been collected as well as the safety profile of the enzyme.…”

Section: Discussionmentioning

confidence: 99%

Enzymatic Inactivation of Endogenous IgG by IdeS Enhances Therapeutic Antibody Efficacy

Järnum

Runström

Bockermann

et al. 2017

Molecular Cancer Therapeutics

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Endogenous plasma IgG sets an immunologic threshold that dictates the activity of tumor-directed therapeutic antibodies. Saturation of cellular antibody receptors by endogenous antibody limits antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Here, we show how enzymatic cleavage of IgG using the bacterial enzyme IdeS can be utilized to empty both high and low affinity Fcgreceptors and clear the entire endogenous antibody pool. Using in vitro models, tumor animal models as well as ex vivo analysis of sera collected during a previous clinical trial with IdeS, we show how clearing of competing plasma antibody levels with IdeS unblocks cellular antibody receptors. We show that therapeutic antibodies against breast cancer (trastuzumab), colon cancer (cetuximab), and lymphomas (rituximab and alemtuzumab) can be potentiated when endogenous IgG is removed. Overall, IdeS is shown to be a potent tool to reboot the human antibody repertoire and to generate a window to preferentially load therapeutic antibodies onto effector cells and thereby create an armada of dedicated tumor-seeking immune cells.

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IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation

Abstract: IdeS reduced or eliminated donor-specific antibodies and permitted HLA-incompatible transplantation in 24 of 25 patients. (Funded by Hansa Medical; ClinicalTrials.gov numbers, NCT02224820 , NCT02426684 , and NCT02475551 .).

Cited by 280 publications

References 29 publications

Advances in the immunology of heart transplantation

Advances in the immunology of heart transplantation

Immunoglobulin G–Degrading Enzyme of Streptococcus pyogenes (IdeS), Desensitization, and the Kidney Allocation System

Enzymatic Inactivation of Endogenous IgG by IdeS Enhances Therapeutic Antibody Efficacy

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