Preliminary in vivo efficacy studies of a recombinant rhesus anti-alpha(4)beta(7) monoclonal antibody.
Recent findings established that primary targets of HIV/SIV are lymphoid cells within the gastrointestinal (GI) tract. Focus has therefore shifted to T-cells expressing alpha(4)beta(7) integrin which facilitates trafficking to the GI tract via binding to MAdCAM-1. Approaches to better understand the role of alpha(4)beta(7)+ T-cells in HIV/SIV pathogenesis include their depletion or blockade of their synthesis, binding and/or homing capabilities in vivo. Such studies can ideally be conducted in rhesus macaques (RM), the non-human primate model of AIDS. Characterization of alpha(4)beta(7) expression on cell lineages in RM blood and GI tissues reveal low densities of expression by NK cells, B-cells, naïve and TEM (effector memory) T-cells. High densities were observed on TCM (central memory) T-cells. Intravenous administration of a single 50mg/kg dose of recombinant rhesus alpha(4)beta(7) antibody resulted in significant initial decline of alpha(4)beta(7)+ lymphocytes and sustained coating of the alpha(4)beta(7) receptor in both the periphery and GI tissues.
Pereira
L E
LE
Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Room 2309 WMB, 101 Woodruff Circle, Atlanta, GA 30322, USA.
Onlamoon
N
N
Wang
X
X
Wang
R
R
Li
J
J
Reimann
K A
KA
Villinger
F
F
Pattanapanyasat
K
K
Mori
K
K
Ansari
A A
AA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology* / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D003430:Cross-Sectional Studies; D005434:Flow Cytometry; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000276:immunology / Q000821:virology; D016023:Integrins / Q000096:biosynthesis / Q000276:immunology*; D008137:Longitudinal Studies; D008253:Macaca mulatta; D008297:Male; D010865:Pilot Projects; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics; D011994:Recombinant Proteins / Q000097:blood / Q000276:immunology / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000821:virology; D014212:Tretinoin / Q000494:pharmacology; D019562:Viral Load
D000911:Antibodies, Monoclonal; D016023:Integrins; D012367:RNA, Viral; D011994:Recombinant Proteins; C071777:integrin alpha4beta7; D014212:Tretinoin