Table 2 Relevant studies of preclinical TNFR2 antagonists/agonists
From: Targeting TNFR2 for cancer immunotherapy: recent advances and future directions
Therapeutic agents | Characteristic | Project status | Clinical indication | Research results | References |
|---|---|---|---|---|---|
MM-401 | TNFR2 agonist | Preclinical | A sample of human ovarian ascites | Upregulates CD8+, CD4+ T surface markers Mediates ADCC and reduces Treg numbers Co-stimulates T cells to promote anti-tumor | |
Y9 | TNFR2 agonist | Preclinical | Multiple types of mouse tumor models | Produces short-term antitumor activity and long-term immune memory Acts through CD8+ T cells and NK cells Promotes proliferation of CD8+ CTL Promotes expression of TNFR2 by Tregs Combination of anti-TNFR2 agonistic antibody with anti-PD-1 or anti-PD-L1 antibody produces better therapeutic effect than combination of anti-PD-1 and anti-CTLA-4 | [15] |
TR75-54.7 | TNFR2 agonist | Preclinical | Bone-marrow transplantation and tumor relapse models KPC cell-derived subcutaneous and orthotopic tumors | The coadministration of a suboptimal number of T cells and an anti-TNFR2 treatment can trigger alloreactivity and subsequently induce a significant antitumor effect. This was associated with a reduced percentage of activated CD4 and CD8 Tregs. Combine with anti-PD-L1eradicated tumors by inhibiting their growth, relieving tumor immunosuppression, and generating robust memory recall. | |
TR75-89 | TNFR2 agonist | Preclinical | CT26 colon cancer model in mice | Inhibits tumor growth and generates durable immune memory Increases CD8+ Teff/Treg ratio Increases IFN-γ synthesis in CD8+ T cells | [135] |
BCG-003 (IC3) | TNFR2 agonist | Preclinical | MC38 colon cancer, B16F10 glioma, and GL261 melanoma models in B-hTNFR2 mice | Reduce tumor volume in multiple tumor models, including colon cancer, glioma, and melanoma models. Enhance the efficacy of PD-1/PD-L1 blocking With ADCC activity, it can promote the proliferation of CD8 + T cells in vitro. The Teff/Treg ratio in tumor microenvironment was significantly increased in vivo. No toxic reaction to human mice. | [148] |
M861 | TNFR2 antagonist | Preclinical | CT26 colon cancer model in mice | Inhibits the proliferation of Tregs cells Better anti-tumor effect in combination with CD25 antibody Decrease Treg activity Promote Teff cell anti-tumor response | [149] |
TY101 | TNFR2 antagonist | Preclinical | CT26 and MC38 colon cancer models in mice | Induces tumor-infiltrating CD4+ Tregs cell death TNFR2 alone has anti-tumor effects Better antitumor effect in combination with multiple drugs Promotes CD8+ CTL survival and enhances its antitumor activity | |
AN3025 | TNFR2 antagonist | Preclinical | TNFR2 humanized mouse model bearing MC38 tumor models | Blocking hTNF-α/hTNFR2 signaling Inhibits Tregs-mediated immunosuppression Promotes Teffs proliferation and IFNγ production Inhibits tumor growth in mice Enhances anti-tumor effects in combination with anti-PD-1 antibody | [151] |
APX601 | TNFR2 antagonist | Preclinical | the mouse Colo205 xenograft models | High affinity with hTNFR2 Blocking immunosuppression of Tregs and MDSCs Depletes TNFR2-expressing Tregs, MDSCs and tumor cells via ADCC and ADCP Anti-tumor activity as a single agent Combination with PD-1 provides more significant tumor suppression | |
TNFR2 antibody | TNFR2 antagonist | Preclinical | Ascites samples from ovarian cancer patients OVCAR3 Ovarian cancer cells Sample of patients with Sezary syndrome | Inhibition of Tregs promotes Teff proliferation. Low effect on healthy human Treg cells and Teffs cells Directly kills TNFR2-expressing cancer cells Restores Tregs/Teff ratio |