Premium
Immune modulation mediated by the humanized anti‐CD70 monoclonal antibody SGN‐70
Author(s) -
Klussman Kerry,
McEarchern Julie A.,
Oflazoglu Ezogelin,
Williams Kacy,
Smith Leia M.,
Nesterova Albina,
Gerber HansPeter,
Grewal Iqbal S.,
Law CheLeung
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.457
Subject(s) - immunology , immune system , cd40 , cd38 , antibody , antigen , monoclonal antibody , medicine , biology , cytotoxic t cell , stem cell , in vitro , cd34 , microbiology and biotechnology , biochemistry
CD70 is a member of the TNF family whose interaction with its cognate receptor CD27 regulates immune effector and memory responses, and blockade of CD70‐CD27 interactions inhibits the onset of EAE and cardiac allograft rejection in mice. Immunohistochemical analysis revealed the presence of CD70+ cells in inflamed tissues of lupus, rheumatoid arthritis and Crohn's disease patients. We have developed a humanized anti‐human CD70 monoclonal antibody, SGN‐70, that can selectively deplete CD70+ antigen‐specific T cells and down‐regulate expression of cytokines and chemokines including IFN‐γ, TNF‐α, VEGF and IP‐10, as well as the co‐stimulatory molecules CD40L, 4‐1BB, ICOS and OX40. In a T‐cell directed co‐stimulation of peripheral blood lymphocyte culture system, SGN‐70 decreased expansion of both T and B cells. The differentiation of CD20+CD38+ peripheral blood B cells to CD20‐CD38+ plasmablasts was also inhibited by SGN‐70, as were levels of secreted Ig. The in vivo activity of SGN‐70 was evaluated in SCID‐huPBMC mice immunized with tetanus toxoid (TT). Treatment with SGN‐70 significantly reduced anti‐TT antibody titers compared to untreated mice or to those that received non‐binding control Ig. Altogether, our data indicate that SGN‐70 can modulate immune responses mediated by both T and B lymphocytes, and provide a rationale to test SGN‐70 clinically in autoimmune indications.