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Transpl Int. 2019 Sep 15. doi: 10.1111/tri.13524. [Epub ahead of print]

Safety and pharmacodynamics of anti-CD2 monoclonal antibody treatment in cynomolgus macaques- an experimental study.

Author information

1
Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, USA.
2
Division of Transplantation Surgery, CLINTEC, Karolinska Institute, and Department of Transplantation Surgery, Karolinska University Hospital, Stockholm, Sweden.
3
Department of Immunology, Genetics and Pathology, Section of Clinical Immunology, Uppsala University, Uppsala, Sweden.
4
MassBiologics, University of Massachusetts Medical School, Boston, MA, USA.
5
Department of Surgery, Columbia University Medical Center, New York, NY, USA.
6
Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY, USA.

Abstract

BACKGROUND:

Anti-CD2 treatment provides targeted immunomodulatory properties that have demonstrated clinical usefulness to condition the immune system and to treat transplant rejection. The treatment is species-specific due to structural CD2 antigen differences between non-human primates and humans. Herein, we report the safety profile and efficacy of two modifications of the same anti-CD2 monoclonal antibody in cynomolgus macaques.

METHODS:

Twelve subjects received one i.v. anti-CD2 (of rat or rhesus type) dose each, range 1-4 mg/kg, and were followed for 1-7 days. Treatment effects were evaluated with flow cytometry on peripheral blood and histopathological evaluation of secondary lymphoid organs. In vitro inhibitory activity on primary MHC disparate MLRs was determined.

RESULTS:

Upon anti-CD2 treatment, CD4+ , CD8+ memory subsets were substantially depleted. Naïve T-cells and Tregs were relatively spared, and exhibited lower CD2 expression than memory T-cells. Early immune reconstitution was noted for naïve cells, while memory counts had not recovered after one week. Both antibodies displayed a concentration-dependent MLR inhibition. Lymph node examination revealed no significant lymphocyte depletion. None of the animals experienced any significant study drug-related adverse events.

CONCLUSIONS:

This study outlines the safety and pharmacodynamic profile of primate-specific anti-CD2 treatment, relevant for translation of anti-CD2-based animal models into clinical trials.

PMID:
31523849
DOI:
10.1111/tri.13524

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