TY - JOUR
T1 - Antibodies targeting human OX40 expand effector T cells and block inducible and natural regulatory T cell function
AU - Voo, Kui S.
AU - Bover, Laura
AU - Harline, Megan L.
AU - Vien, Long T.
AU - Facchinetti, Valeria
AU - Arima, Kazuhiko
AU - Kwak, Larry W.
AU - Liu, Yong J.
PY - 2013/10/1
Y1 - 2013/10/1
N2 - Current cancer vaccines induce tumor-specific T cell responses without sustained tumor regression because immunosuppressive elements within the tumor induce exhaustion of effector T cells and infiltration of immune-suppressive regulatory T cells (Tregs). Therefore, much effort has been made to generate agonistic Abs targeting members of the TNFR superfamily, such as OX 40, 4-1BB, and GITR, expressed on effector T cells and Tregs, to reinvigorate T cell effector function and block Treg-suppressive function. In this article, we describe the development of a panel of anti-human OX40 agonistic mouse mAbs that could promote effector CD4+ and CD8+ T cell proliferation, inhibit the induction of CD4+ IL-10 -producing type 1 regulatory T cells, inhibit the expansion of ICOS+IL-10+ Tregs, inhibit TGF-β-induced FOXP3 expression on naive CD4+ T cells, and block natural Treg-suppressive function. We humanized two anti-human OX40 mAb clones, and they retained the potency of their parental clones. These Abs should provide broad opportunities for potential combination therapy to treat a wide realm of cancers and preventative vaccines against infectious diseases.
AB - Current cancer vaccines induce tumor-specific T cell responses without sustained tumor regression because immunosuppressive elements within the tumor induce exhaustion of effector T cells and infiltration of immune-suppressive regulatory T cells (Tregs). Therefore, much effort has been made to generate agonistic Abs targeting members of the TNFR superfamily, such as OX 40, 4-1BB, and GITR, expressed on effector T cells and Tregs, to reinvigorate T cell effector function and block Treg-suppressive function. In this article, we describe the development of a panel of anti-human OX40 agonistic mouse mAbs that could promote effector CD4+ and CD8+ T cell proliferation, inhibit the induction of CD4+ IL-10 -producing type 1 regulatory T cells, inhibit the expansion of ICOS+IL-10+ Tregs, inhibit TGF-β-induced FOXP3 expression on naive CD4+ T cells, and block natural Treg-suppressive function. We humanized two anti-human OX40 mAb clones, and they retained the potency of their parental clones. These Abs should provide broad opportunities for potential combination therapy to treat a wide realm of cancers and preventative vaccines against infectious diseases.
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U2 - 10.4049/jimmunol.1202752
DO - 10.4049/jimmunol.1202752
M3 - Article
C2 - 24014877
AN - SCOPUS:84885121967
SN - 0022-1767
VL - 191
SP - 3641
EP - 3650
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -