Table Info

Table 2.

Overview of TGF-β signaling immunotherapies

Type	Treatment	Mechanism	Status	Reference
Antibodies	Fresolimumab	Neutralization of TGF-β1, TGF-β2 and TGF-β3	Phase II	[124]
	NIS793	Neutralization of pan TGF-β ligands	Phase II	[125]
	SAR439459	Neutralization of TGF-β1, TGF-β2 and TGF-β3	Phase I/II	[126]
	TβM1 (LY2382770)	Selective neutralization of TGF-β1	Phase I	[127]
	XPA-42-089	Blockage of TGF-β1 and TGF-β2	Preclinical	[125]
	ABBV-151	Blockage of the GARP-TGF-β1 complex and the release of TGF-β1	Preclinical	[128]
	Anti-LAP	Reducing the latent release of inactive TGF-β from LAP/TGF-β complex	Phase I	[129]
	264RAD	Inhibition on αvβ6 and αvβ8 integrin	Preclinical	[130]
	Anti-αVβ8 (ADWA-11)	Neutralization of αVβ8	Preclinical	[131]
	Anti-αVβ8 (C6D4)	Neutralization of αVβ8	Preclinical	[132]
	SRK-181	Binding to latent TGF-β to prevent its activation	Phase I	[133]
	IMC-TR1 (LY3022859)	Inhibition on TβRII	Phase I	[134]
ASOs	ISTH0036	Selective inhibition on TGF-β2 mRNA	Phase I	[140]
	ISTH0047 or ISTH1047	Reduction of TGF-β1 or TGF-β2 expression	Preclinical	[141]
	Trabedersen (AP 12009)	Inhibition on TGF-β2 expression	Phase I/II/III	[143]
Bifunctional fusion protein	4T-Trap	Binding to CD4 and inhibiting Th cell TGF-β signaling	Preclinical	[147]
	AVID200	Neutralization of TGF-β1 and TGF-β3	Phase I	[148]
	Bintrafusp alfa (M7824)	Reduction in expression of TGF-β and blockage of PD-L1 on CD8⁺ T cells	Phase II/III	[149]
	SHR-1701	Blockage of TGF-β/TβR pathway and rescue on PD-1/PD-L1 pathway	Phase I	[152]
	sTβRII-Fc	Inhibition on TGF-β1-dependent Smad3 phosphorylation	Preclinical	[154]
	Soluble β-glycan/TβRIII	Activating the TGF-β2-Smad signaling and the expression of TβRIII	Preclinical	[157]
Small-molecule inhibitors	AZ12601011, AZ12799734	Inhibition on TβRI-mediated phosphorylation of Smad2 and BMP pathway	Preclinical	[160]
	Galunisertib (LY2157299)	Inhibition on TβRI-mediated phosphorylation of Smad2	Phase I/II	[161]
	GFH-018	Inhibition on TβRI	Phase I/II	[165]
	LY3200882	Competitive inhibition on the serine-threonine kinase domain of TβRI	Phase I/II	[167]
	PF-06952229	Inhibition on TβRI	Phase I	[169]
	SB431542	Inhibition on TβRI	Preclinical	[171]
	SD-208	Inhibition on both TβRI and TβRII	Preclinical	[171]
	TD-1058	Inhibition on TβRI	Phase I	[178]
	Vactosertib (TEW7197)	Inhibition on TβRI	Phase I/II	[172]
	YL-13027	Inhibition on TβRI	Phase I	[175]
TCVs	Belagenpumatucel-L	Expressing the antisense strand of the TGF-β2 to suppress the expression of TGF-β2	Phase II/III	[181]
TCVs	Gemogenovatucel-T	Suppression on TGF-β1 and TGF-β2 levels by a furin-targeting RNA	Phase II	[182]

Declarations

Author contributions

MKKC and ELYC equally contributed to: Conceptualization, Investigation, Writing—original draft, Writing—review & editing, Visualization. ZZJ, ASWC: Investigation, Data curation, Writing—review & editing. CL, KTL, KFT: Conceptualization, Methodology. PMKT: Conceptualization, Writing—original draft, Writing—review & editing, Visualization.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

This study was supported by the Research Grants Council of Hong Kong [RGC 14106518, 14111019, 14111720] RGC Postdoctoral Fellowship Scheme [PDFS2122-4S06] Health and Medical Research Fund [10210726] The Chinese University of Hong Kong’s Faculty Innovation Award [4620528], Direct Grant for Research [4054510, 4054668], Postdoctoral Fellowship Scheme [NL/LT/PDFS2022/0360/22lt], CU Medicine Passion for Perfection Scheme [PFP202210-004] and Global Physician-Leadership Stream programme. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

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