Journal
TRANSPLANT INTERNATIONAL
Volume 33, Issue 1, Pages 98-107Publisher
WILEY
DOI: 10.1111/tri.13524
Keywords
anti-CD2; induction; large animal models; monoclonal antibody; tolerance
Categories
Funding
- NCATS NIH HHS [UL1 TR001873] Funding Source: Medline
- NCI NIH HHS [P30 CA013696] Funding Source: Medline
- NIAID NIH HHS [R56 AI122332, U24 AI126683] Funding Source: Medline
- NIDDK NIH HHS [P30 DK063608, R01 DK064819] Funding Source: Medline
- NIH HHS [R24 OD010976, UL1TR001873] Funding Source: Medline
- NIH Nonhuman Primate Reagent Resource [U24AI126683, R24OD010976] Funding Source: Medline
- Diabetes and Endocrinology Research Center Flow Core Facility funded in part through Center Grant [5P30DK063608] Funding Source: Medline
- Herbert Irving Comprehensive Cancer Center Flow Cytometry Shared Resources funded in part through Center Grant [P30CA013696] Funding Source: Medline
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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. Naive T cells and Tregs were relatively spared and exhibited lower CD2 expression than memory T cells. Early immune reconstitution was noted for naive 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.
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