A new study is suggesting that a new targeted therapy approach may have the potential to boost antitumor immune responses and directly kill tumor cells.
Investigators at Massachusetts General Hospital (MGH) have discovered that tumor necrosis factor receptor type II (TNFR2) may be a new target for cancer immunotherapies. TNFR2 is expressed on many types of cancer cells and on immunosuppressive regulatory T cells (Tregs) that infiltrate tumors and suppress immune system activity. The researchers report in Science Signaling on the potential of using TNFR2 antagonists as new targeted therapy.1 They write that by targeting tumor cells and immunosuppressive tumor-associated Tregs, it may be possible to use antagonistic TNFR2 antibodies as an effective treatment for cancers positive for TNFR2.
The researchers describe how it may be possible to simultaneously block an immune checkpoint molecule in T cells and an oncoprotein in tumor cells. The MGH team characterized the effects of inhibiting TNFR2 activation using antagonistic monoclonal antibodies that block rather than stimulate activation of the receptor. They demonstrated that these antibodies inhibited the proliferation of T regulatory cells, allowing a restoration of host immunity in vivo. The TNFR2 antibodies more potently killed Tregs isolated from fluid surrounding ovarian cancer metastases than Tregs from cancer-free individuals, suggesting that TNFR2-expressing Tregs are unique to the tumor microenvironment. These antagonistic antibodies also directly killed cells from a TNFR2-expressing ovarian cancer cell line.
p<1. Torrey H, Butterworth J, Mera T, et al. Targeting TNFR2 with antagonistic antibodies inhibits proliferation of ovarian cancer cells and tumor-associated Tregs. Sci Signal. 2017 Jan 17;10(462). doi: 10.1126/scisignal.aaf8608