Native-like TNFSF trimer proteins supporting next-generation therapeutics

Functional classification of TNF superfamily members, image via Sino Biological

TNF superfamily (TNFSF) proteins are key regulators of immune homeostasis and inflammation. Many TNFSF proteins naturally assemble as homotrimers, a structural feature that is critical for receptor binding and downstream signaling

Members such as TNF-α, BAFF, TL1A, RANKL and CD70 play critical roles in immune activation, B-cell function, inflammatory signaling, and tumor immunity. Their central roles in these pathways have made them attractive targets for the development of novel biologics, immunotherapies, and next-generation therapeutic modalities. Sino Biological offers high-quality, native-like TNFSF trimer proteins to support therapeutic target research and drug discovery.

Translational and Clinical Validation of TNFSF Targeting

The clinical success of TNFSF-targeted therapies highlights the importance of accurately modeling TNFSF biology during target validation, antibody discovery, and therapeutic development. Landmark therapies targeting TNF-α and RANKL have demonstrated the therapeutic value of TNFSF family members across chronic inflammatory diseases, bone disorders, and immune-mediated conditions, establishing TNFSF proteins as a clinically validated target class. 

More recently, BAFF-, TL1A-, and CD70-directed therapeutics have further expanded the clinical impact of TNFSF-targeted interventions in autoimmune diseases and cancer. BAFF-targeted therapies have demonstrated efficacy in systemic lupus erythematosus, while TL1A- and CD70-directed therapeutics have gained significant attention as promising approaches for inflammatory bowel disease and cancer. Together, these advances underscore the growing translational and therapeutic significance of TNFSF-targeted drug development.

Table 1. Representative TNFSF-targeted therapeutics and clinical development programs.

TNFSF MemberMajor IndicationsRepresentative Therapeutic ProgramsDevelopment Status
TNF-α (TNFSF2)Rheumatoid arthritis, psoriasis, IBDHumira, Remicade, EnbrelApproved
BAFF (TNFSF13B)Systemic lupus erythematosusBenlystaApproved
APRIL (TNFSF13)Multiple myeloma, autoimmune diseasesAtaciceptLate-stage clinical
CD40L (TNFSF5)Autoimmune diseases, transplantationDapirolizumab pegolPhase III
CD70 (TNFSF7)Hematologic malignancies, solid tumorsADCs, TCEs, CAR-T therapiesClinical development
4-1BBL (TNFSF9)Cancer immunotherapy4-1BB agonist programsClinical development
OX40L (TNFSF4)Autoimmune diseases, cancerOX40/OX40L-targeted antibodiesClinical development
TRAIL (TNFSF10)Solid tumors, hematologic malignanciesTRAIL receptor agonistsClinical development
RANKL (TNFSF11)Osteoporosis, bone metastasisProlia (denosumab), XgevaApproved
TL1A (TNFSF15)Inflammatory bowel diseaseMK-7240, RVT-3101Phase III

Research Applications of Native-Like TNFSF Trimer Proteins

Native-like trimeric TNFSF proteins enable biologically relevant receptor engagement and downstream signaling. For example, recombinant human TNF-α protein (Cat# 10602-HNAE) and cynomolgus/rhesus TNF-α protein (Cat# 90018-CNAE) were used by Dave et al. to characterize antibody–antigen complex formation in a DLS assay (Figure 2). In another study, recombinant human RANKL protein (Cat# 11682-HNCH) was used to induce osteoclast differentiation from human PBMCs in the presence of M-CSF, supporting bone remodeling and osteoporosis research (Figure 3).

Figure 1. Antibody: antigen complex formation with individual or combined antigen addition. DLS was used to measure the complex volumes (nm3) formed by TrYbe, DVD-IgG, and FynomAb when combined at defined molar ratios with (a, i) TNF, (b, i) IL-17A, or (c, i) both TNF and IL-17A. Panels (ii) display magnified views of the corresponding plots (a–c) to highlight the smaller complexes formed by TrYbe and FynomAb, where applicable.

Source: https://doi.org/10.1080/19420862.2022.2160229

Figure 2. Human PBMCs were stimulated with recombinant human RANKL and M-CSF to induce osteoclast differentiation. Representative TRAP staining images show the formation of multinucleated osteoclasts under RANKL-induced conditions. 

Source: https://doi.org/10.1038/s41467-025-66285-8

Sino Biological Native-Like TNFSF Trimer Proteins

Sino Biological provides a comprehensive portfolio of high-quality, native-like TNFSF trimer proteins to accelerate therapeutic target research and drug discovery. By preserving the native trimeric structure required for efficient receptor activation and downstream signaling, these recombinant proteins enable biologically relevant experimental models for antibody discovery, functional characterization, and translational research. Each product is rigorously validated for purity and biological activity using orthogonal analytical and functional assays, ensuring high quality, batch-to-batch consistency, and reproducible experimental results.

Validated Native-Like TNFSF Trimer Proteins 

MoleculeCat#SpeciesPurity VerifiedActivity Validated
TL1A (TNFSF15)17049-H07H2HumanSDS-PAGE, SEC-MALSSPR
TL1A (TNFSF15)5A7685-M07H1-UEMouseSDS-PAGE, SEC-MALSSPR
BAFF (TNFSF13B)10056-HNCHHumanSDS-PAGE, SEC-HPLCCell-based assay
BAFF (TNFSF13B)10056-H42H-BHumanSDS-PAGE, SEC-MALSELISA
APRIL (TNFSF13)10610-H07H2HumanSDS-PAGE, SEC-MALSSPR
APRIL (TNFSF13)91072-C01HHumanSDS-PAGE, SEC-MALSSPR
CD70 (TNFSF7)10780-H07H5HumanSDS-PAGE, SEC-HPLCELISA
CD70 (TNFSF7)51129-M07H2MouseSDS-PAGE, SEC-HPLCELISA
RANKL (TNFSF11)11682-HNCHHumanSDS-PAGE, SEC-MALSCell-based assay
OX40L (TNFSF4)13127-H07HHumanSDS-PAGE, SEC-MALSELISA
OX40L (TNFSF4)13127-H07H-BHumanSDS-PAGE, SEC-MALSELISA

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