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 nonhuman primates and humans. Herein, we report the safety profile and efficacy of two modifications of the same anti-CD2 monoclonal antibody in cynomolgus macaques. 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 mixed lymphocyte reactions (MLRs) was determined. 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. 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.
Keywords: anti-CD2; induction; large animal models; monoclonal antibody; tolerance.
© 2019 Steunstichting ESOT.
Conflict of interest statement
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- U24 AI126683/AI/NIAID NIH HHS/United States
- R24OD010976/NIH Nonhuman Primate Reagent Resource
- P30CA013696/Herbert Irving Comprehensive Cancer Center Flow Cytometry Shared Resources funded in part through Center Grant
- U24AI126683/NIH Nonhuman Primate Reagent Resource
- UL1 TR001873/TR/NCATS NIH HHS/United States
- P30 DK063608/DK/NIDDK NIH HHS/United States
- UL1TR001873/NH/NIH HHS/United States
- R24 OD010976/OD/NIH HHS/United States
- P30 CA013696/CA/NCI NIH HHS/United States
- 5P30DK063608/Diabetes and Endocrinology Research Center Flow Core Facility funded in part through Center Grant
- R56 AI122332/AI/NIAID NIH HHS/United States