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

Erik Berglund, Paula Alonso-Guallart, Makenzie Danton, Felix Sellberg, Christian Binder, Robin Fröbom, David Berglund, Nathaly Llore, Hiroshi Sakai, Alina Iuga, Dilrukshi Ekanayake-Alper, Keith A Reimann, David H Sachs, Megan Sykes, Adam Griesemer
Transplant International 2019 September 15

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.

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