Dataset Information

Antibodies targeting human OX40 expand effector T cells and block inducible and natural regulatory T cell function.

ABSTRACT: 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-?-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.

SUBMITTER: Voo KS

PROVIDER: S-EPMC3812678 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Antibodies targeting human OX40 expand effector T cells and block inducible and natural regulatory T cell function.

Voo Kui S KS Bover Laura L Harline Megan L ML Vien Long T LT Facchinetti Valeria V Arima Kazuhiko K Kwak Larry W LW Liu Yong J YJ

Journal of immunology (Baltimore, Md. : 1950) 20130906 7

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 ...[more]

PMID: 24014877

Similar Datasets

Project description:The ability to profile the prevalence and functional activity of endogenous antibodies is of vast clinical and diagnostic importance. Serum antibodies are an important class of biomarkers and are also crucial elements of immune responses elicited by natural disease-causing agents as well as vaccines. In particular, materials for manipulating and/or enhancing immune responses toward disease-causing cells or viruses have exhibited significant promise for therapeutic applications. Antibody-recruiting molecules (ARMs), bifunctional organic molecules that redirect endogenous antibodies to pathological targets, thereby increasing their recognition and clearance by the immune system, have proven particularly interesting. Notably, although ARMs capable of hijacking antibodies against oligosaccharides and electron-poor aromatics have proven efficacious, systematic comparisons of the prevalence and effectiveness of natural anti-hapten antibody populations have not appeared in the literature. Herein we report head-to-head comparisons of three chemically simple antigens, which are known ligands for endogenous antibodies. Thus, we have chemically synthesized bifunctional molecules containing 2,4-dinitrophenyl (DNP), phosphorylcholine (PC), and rhamnose. We have then used a combination of ELISA, flow cytometry, and cell-viability assays to compare these antigens in terms of their abilities both to recruit natural antibody from human serum and also to direct serum-dependent cytotoxicity against target cells. These studies have revealed rhamnose to be the most efficacious of the synthetic antigens examined. Furthermore, analysis of 122 individual serum samples has afforded comprehensive insights into population-wide prevalence and isotype distributions of distinct anti-hapten antibody populations. In addition to providing a general platform for comparing and studying anti-hapten antibodies, these studies serve as a useful starting point for the optimization of antibody-recruiting molecules and other synthetic strategies for modulating human immunity.

Dataset Information

Antibodies targeting human OX40 expand effector T cells and block inducible and natural regulatory T cell function.

Publications

Antibodies targeting human OX40 expand effector T cells and block inducible and natural regulatory T cell function.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets