Research ArticleCancer Immunotherapy

Targeting TNFR2 with antagonistic antibodies inhibits proliferation of ovarian cancer cells and tumor-associated Tregs

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Sci. Signal.  17 Jan 2017:
Vol. 10, Issue 462, eaaf8608
DOI: 10.1126/scisignal.aaf8608

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Killing ovarian cancer by trapping TNFR2

Signaling by tumor necrosis factor (TNF) family promotes tumor growth and progression. The TNF receptor 2 (TNFR2) is present on the surface of immunosuppressive regulatory T cells and some tumor cells. Torrey et al. (see coverage by Chen and Oppenheim) developed antibodies that bind and lock TNFR2 in an inactive conformation. The antibodies killed ovarian cancer cells in culture. Additionally, the antibodies inhibited the proliferation of regulatory T cells while promoting the proliferation of effector T cells isolated from metastatic sites (ascites) in ovarian cancer patients. The antibodies had less of an effect on T cells isolated from the peripheral blood of normal donors. Thus, these antibodies may be more specific and less toxic than current TNFR antibodies, providing a new path for treating ovarian cancer.