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 Member Major Indications Representative Therapeutic Programs Development Status TNF-α (TNFSF2) Rheumatoid arthritis, psoriasis, IBD Humira, Remicade, Enbrel Approved BAFF (TNFSF13B) Systemic lupus erythematosus Benlysta Approved APRIL (TNFSF13) Multiple myeloma, autoimmune diseases Atacicept Late-stage clinical CD40L (TNFSF5) Autoimmune diseases, transplantation Dapirolizumab pegol Phase III CD70 (TNFSF7) Hematologic malignancies, solid tumors ADCs, TCEs, CAR-T therapies Clinical development 4-1BBL (TNFSF9) Cancer immunotherapy 4-1BB agonist programs Clinical development OX40L (TNFSF4) Autoimmune diseases, cancer OX40/OX40L-targeted antibodies Clinical development TRAIL (TNFSF10) Solid tumors, hematologic malignancies TRAIL receptor agonists Clinical development RANKL (TNFSF11) Osteoporosis, bone metastasis Prolia (denosumab), Xgeva Approved TL1A (TNFSF15) Inflammatory bowel disease MK-7240, RVT-3101 Phase 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
Molecule Cat# Species Purity Verified Activity Validated TL1A (TNFSF15) 17049-H07H2 Human SDS-PAGE, SEC-MALS SPR TL1A (TNFSF15) 5A7685-M07H1-UE Mouse SDS-PAGE, SEC-MALS SPR BAFF (TNFSF13B) 10056-HNCH Human SDS-PAGE, SEC-HPLC Cell-based assay BAFF (TNFSF13B) 10056-H42H-B Human SDS-PAGE, SEC-MALS ELISA APRIL (TNFSF13) 10610-H07H2 Human SDS-PAGE, SEC-MALS SPR APRIL (TNFSF13) 91072-C01H Human SDS-PAGE, SEC-MALS SPR CD70 (TNFSF7) 10780-H07H5 Human SDS-PAGE, SEC-HPLC ELISA CD70 (TNFSF7) 51129-M07H2 Mouse SDS-PAGE, SEC-HPLC ELISA RANKL (TNFSF11) 11682-HNCH Human SDS-PAGE, SEC-MALS Cell-based assay OX40L (TNFSF4) 13127-H07H Human SDS-PAGE, SEC-MALS ELISA OX40L (TNFSF4) 13127-H07H-B Human SDS-PAGE, SEC-MALS ELISA