Table 2.

Relevant studies of preclinical TNFR2 antagonists/agonists

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	[145, 146]
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.	[12, 135, 147]
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	[17, 150]
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	[152, 153]
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	[108, 154]