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The TNFRs OX40, 4-1BB, and CD40 as targets for cancer immunotherapy.

ABSTRACT: T cell-mediated rejection of tumors requires signals from the T cell receptor and co-stimulatory molecules to license effector functions of tumor-antigen specific T cells. There is also an array of immune suppressive mechanisms within the tumor microenvironment that can suppress anti-tumor immunity. The use of monoclonal antibodies to overcome this suppression and/or enhance tumor-antigen specific T cell responses has shown promise in clinical trials. In particular, targeting co-stimulatory members of the tumor necrosis factor receptor (TNFR) family with agonist Abs enhances T cell function, which has led to encouraging therapeutic results in cancer-bearing hosts. These encouraging data establish TNFRs as important targets for enhancing tumor-specific immune responses in mice and man. This review will focus on agonists that target the TNFRs OX40, 4-1BB, and CD40.

SUBMITTER: Moran AE

PROVIDER: S-EPMC3815601 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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The TNFRs OX40, 4-1BB, and CD40 as targets for cancer immunotherapy.

Moran Amy E AE Kovacsovics-Bankowski Magdalena M Weinberg Andrew D AD

Current opinion in immunology 20130214 2

T cell-mediated rejection of tumors requires signals from the T cell receptor and co-stimulatory molecules to license effector functions of tumor-antigen specific T cells. There is also an array of immune suppressive mechanisms within the tumor microenvironment that can suppress anti-tumor immunity. The use of monoclonal antibodies to overcome this suppression and/or enhance tumor-antigen specific T cell responses has shown promise in clinical trials. In particular, targeting co-stimulatory memb ...[more]

PMID: 23414607

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