Phase I/II trial of a combination of anti-CD3/CD7 immunotoxins for steroid-refractory acute graft-versus-host disease

Christoph Groth, Lenneke F J van Groningen, Tiago R Matos, Manita E Bremmers, Frank W M B Preijers, Harry Dolstra, Christian Reicherts, Nicolaas P M Schaap, Eric H G van Hooren, Joanna IntHout, Mihai G Netea, Rosalinde Masereeuw, John E Levine, George Morales, James L Ferrara, Nicole M A Blijlevens, Ypke V J M van Oosterhout, Matthias Stelljes, Walter J F M van der Velden

Research output: Contribution to journalArticleAcademicpeer-review


Effective therapies for treating patients with steroid-refractory acute graft-versus-host-disease (SR-aGvHD), particularly strategies that reduce the duration of immunosuppression following remission, are urgently needed. The investigated immunotoxin-combination consists of a mixture of anti-CD3 and anti-CD7 antibodies separately conjugated to recombinant ricin A (CD3/CD7-IT), which induces in-vivo depletion of T- and NK-cells and suppresses T-cell receptor activation. We conducted a phase I/II trial in order to examine the safety and efficacy of CD3/CD7-IT in 20 patients with SR-aGvHD; 17 of these patients (85%) had severe SR-aGvHD, and all 20 patients had visceral organ involvement; 18 gastrointestinal (GI) (90%) and 5 liver (25%) involvement. A validated two biomarker algorithm classified the majority of patients (11/20) as high-risk. On day 28 after the start of CD3/CD7-IT, the overall response rate was 60% (12/20), with 10 patients (50%) achieving a complete response; moreover, the 6-month overall survival rate was 60% (12/20), including 64% (7/11) classified as high risk by biomarkers. The one-week treatment course with CD3/CD7-IT caused profound but transient depletion of T- and NK-cells, followed by rapid recovery of the immune system with a diverse TCR Vβ repertoire, and preservation of EBV- and CMV-specific T-cell clones. Furthermore, our results indicate that CD3/CD7-IT appeared to be safe and well-tolerated, with a relatively low prevalence of manageable and reversible adverse events, primarily worsening of hypoalbuminemia, microangiopathy, and thrombocytopenia. These encouraging results suggest that CD3/CD7-IT may improve patient outcomes in patients with SR-aGVHD. This trial was registered at as #NCT02027805.

Original languageEnglish
Pages (from-to)712-719
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Issue number4
Publication statusPublished - Apr 2019


  • Immunotoxin
  • Acute graft-versus-host disease
  • Allogenic hematopoietic stem cell transplantation


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