Pharmacokinetic and pharmacodynamic study of a clinically effective anti-CD2 monoclonal antibody.
Animals
Antibodies, Monoclonal
/ pharmacokinetics
Antibodies, Monoclonal, Humanized
/ pharmacokinetics
Biomarkers
Biopsy
CD2 Antigens
/ antagonists & inhibitors
Cytokines
/ blood
Female
Immunoglobulin G
/ administration & dosage
Immunophenotyping
Killer Cells, Natural
/ immunology
Lymphocyte Depletion
Lymphocytes
/ immunology
Male
Pan troglodytes
Rats
antibodies/immunoglobulins
experimental animals
molecules
processes
solid organ transplantation
subject
transplantation
Journal
Scandinavian journal of immunology
ISSN: 1365-3083
Titre abrégé: Scand J Immunol
Pays: England
ID NLM: 0323767
Informations de publication
Date de publication:
Jan 2020
Jan 2020
Historique:
received:
08
08
2019
revised:
14
10
2019
accepted:
15
10
2019
pubmed:
21
10
2019
medline:
15
1
2020
entrez:
21
10
2019
Statut:
ppublish
Résumé
The humanized IgG1κ monoclonal antibody siplizumab and its rat parent monoclonal IgG2b antibody BTI-322 are directed against the CD2 antigen. Siplizumab is species-specific, reacting with human and chimpanzee cells but not with cells from any other species, including other non-human primates. Because siplizumab treatment has recently shown great potential in clinical transplantation, we now present the results of our previous pharmacokinetic, pharmacodynamic and safety studies of both antibodies. Fourteen chimpanzees received 1-3 doses of 0.143 to 5.0 mg/kg iv The effects were followed with flow cytometry on peripheral lymphocytes and staining of lymph nodes. Side effects were recorded. Serum antibody concentrations were followed. Across the doses, a rapid, transient depletion of CD2, CD3, CD4 and CD8 lymphocytes and NK cells was observed for both antibodies. Immune reconstitution was more rapid for BTI-322 compared to siplizumab. Paracortical lymph node T cell depletion was moderate, estimated at 45% with doses of >0.6 mg/kg. Restoration of lymph node architecture was seen after two weeks to two months for all animals. All four subjects receiving BTI-322 experienced AEs on the first dosing day, while the eight subjects dosed with siplizumab experienced few mild, transient AEs. Infusion with siplizumab and BTI-322 resulted in rapid depletion of CD2
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Monoclonal, Humanized
0
Biomarkers
0
CD2 Antigens
0
Cytokines
0
Immunoglobulin G
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12839Informations de copyright
© 2019 The Scandinavian Foundation for Immunology.
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