2020
DOI: 10.1158/1538-7445.am2020-936
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Abstract 936: Targeting TNFR2 for cancer immunotherapy: Ligand blocking depletors versus receptor agonists

Abstract: The pleiotropic TNF-α:TNFR axis plays a central role in the immune system. While the cellular expression of TNFR1 is broad, TNFR2 expression is mainly restricted to immune cells and especially high on T regs. The therapeutic potential of targeting TNFR2 for cancer treatment has been previously indicated but the mechanism-of-action (MoA) of these reagents remains unclear, with conflicting data reported by different investigators. To gain further insight, we identified and characterized a wide panel of human and… Show more

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Cited by 8 publications
(14 citation statements)
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“…They reported an antitumor effect on several cancer types using the murine version and found corresponding activity of human agonist TNFR2 antibodies that could be used in patients. • Encouraging unpublished results were also presented at the AACR annual meetings in 2020 and 2021, regarding advances in both agonists and antagonists targeting TNFR2 and tested in the context of cancer (Mårtensson et al, 2020;Chen et al, 2021).…”
Section: Therapeutic Perspectives Current State Of Clinical-grade Therapeutic Toolsmentioning
confidence: 99%
See 1 more Smart Citation
“…They reported an antitumor effect on several cancer types using the murine version and found corresponding activity of human agonist TNFR2 antibodies that could be used in patients. • Encouraging unpublished results were also presented at the AACR annual meetings in 2020 and 2021, regarding advances in both agonists and antagonists targeting TNFR2 and tested in the context of cancer (Mårtensson et al, 2020;Chen et al, 2021).…”
Section: Therapeutic Perspectives Current State Of Clinical-grade Therapeutic Toolsmentioning
confidence: 99%
“…Encouraging unpublished results were also presented at the AACR annual meetings in 2020 and 2021, regarding advances in both agonists and antagonists targeting TNFR2 and tested in the context of cancer ( Mårtensson et al, 2020 ; Chen et al, 2021 ).…”
Section: Therapeutic Perspectivesmentioning
confidence: 99%
“…BI-1910 is another agonist anti-TNFR2 mAb in development following promising results from a surrogate anti-mouse TNFR2 antibody; this mAb induced strong anti-tumor responses in several pre-clinical tumor models and was effectively combined with checkpoint blockade antibodies. The dominant mechanism of action was expansion of CD8 + T cells and improved CD8 + to Treg ratio in the tumor site ( 143 ). BI-1808 is an alternative TNFR2 targeting mAb, classified as a deleting, ligand blocking molecule.…”
Section: Targeting Tnfr2mentioning
confidence: 99%
“…In a preclinical study, the anti-TNFR2 antibody BI-1808 demonstrated potent antitumor efficacy in CT26, MC38, and B16 cancer models as a single agent or in combination with an anti-PD-1 antibody. BI-1808 depleted early tumor-infiltrating Tregs and induced promotion of Teffs at the tumor site, which improved the ratio of CD8 + Teffs to Tregs and tumor regression ( 95 ). Currently, BI-1808 is being studied in Phase I/II clinical trials.…”
Section: Antibody-based Immunotherapies Targeting Tumor-infiltrating ...mentioning
confidence: 99%