Antibodies Targeting Human OX40 Expand Effector T Cells and Block Inducible and Natural Regulatory T Cell Function

作者：Voo, Kui S.; Bover, Laura; Harline, Megan L.; Vien, Long T.; Facchinetti, Valeria; Arima, Kazuhiko; Kwak, Larry W.; Liu, Yong J.^*

来源：The Journal of Immunology, 2013, 191(7): 3641-3650.

DOI：10.4049/jimmunol.1202752

• IMMUNOLOGICAL SELF-TOLERANCE
• FOSTERS IMMUNE PRIVILEGE
• TGF-BETA
• ANTITUMOR IMMUNITY
• CD4(+) CD25(+)
• TUMOR
• ANTIGEN
• SUPPRESSION
• MELANOMA
• SURVIVAL

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 OX40, 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-beta-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.

• 出版日期2013-10-1