Preliminary in vivo efficacy studies of a recombinant rhesus anti-α4β7 monoclonal antibody1

• Published in: Cellular immunology Vol. 259; no. 2; pp. 165 - 176
• Main Authors: Pereira, L. E., Onlamoon, N., Wang, X., Wang, R., Li, J., Reimann, K. A., Villinger, F., Pattanapanyasat, K., Mori, K., Ansari, A. A.
• Format: Journal Article
• Language: English
• Published: 01-01-2009
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2009.06.012

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 α
4
β
7
integrin which facilitates trafficking to the GI tract via binding to MAdCAM-1. Approaches to better understand the role of α
4
β
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 α
4
β
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 50 mg/kg dose of recombinant rhesus α
4
β
7
antibody resulted in significant initial decline of α
4
β
7
+ lymphocytes and sustained coating of the α
4
β
7
receptor in both the periphery and GI tissues.