4-1BBL (Aglyco-Fc-Fusion)
4-1BBL (Aglyco-Fc-Fusion)
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The 4-1BBL can induce anti-tumor activities by promoting CD8 T cell expansion and protect against autoimmunity and transplantation rejection by depletion NK and B cells. The 4-1BB/4-1BBL pathway is a potential therapeutic target for oncology and autoimmune disorders.
Interacting protein(s): 4-1BB
Related products: Hexa-Ligand
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Quick Spec
| Species: | Human |
| Catalog No.: | P7118G |
| Synonym: | CD137L, TNFSF9 |
| Tag: | Aglycosylated mouse IgG2a Fc |
| GenBank Accession: | NM_003811 |
| SwissPro Accession: | P41273 |
| Expression Host: | 293T |
| Construction: | Aglycosylated mouse IgG2a Fc-GIL-Human 4-1BBL (A50–E254)-AAL |
| MW (calculated): | 48287 daltons |
| MW (SDS-PAGE): | 52 Kd |
| Abs 0.1% (= 1 mg/ml): | 1.147 |
| Purity: | 95 % |
Description
Murine 4-1BB ligand was initially cloned by expression cloning form a cDNA library of EL4 thymoma cells using 4-1BB-Fc fusion protein. The 4-1BB Ligand is a member of the TNF superfamily (TNFSF). It carboxyl terminal extracellular domain contains three N-glycosylation sites. In addition, its membrane proximal region is rich in threonine, serine and proline residues which is indicative of O-linked glycosylation site.
Interestingly, both human and mouse 4-1BB ligand are among the least homologous member of the TNF superfamily. While earlier studies indicated that 4-1BB ligand might be an exception within the TNFSF and exists as dimeric protein. Subsequent studies shows the soluble trimeric ligand interacts with 4-1BB just like other TNFSF/TNFRSF pairs.
The anti-tumor effect of the 4-1BB/4-1BBL axis is based on the observation that 4-1BBL stimulates activated T cells, particularly CD8 T cells and induces secretion of high levels of IFN-g even though the potential adverse effects of inducing autoimmune status has to be considered at all time. Interestingly, in vivo administration of agonistic anti-4-1BB antibody leads to depletion of B, NK, and CD4 T cells. Hence, 4-1BBL can promote CD8 T cell expansion as well as protect against autoimmune and transplantation rejection. The 4-1BB/4-1BBL pathway is an important therapeutic candidate for oncology.
Amino Acid Sequence
References
1. Salek-Ardakani S, Zajonc DM, Croft M. Agonism of 4-1BB for immune therapy: a perspective on possibilities and complications. Front Immunol. 2023;14:1228486. Epub 20230817. doi: 10.3389/fimmu.2023.1228486. PubMed PMID: 37662949; PubMed Central PMCID: PMC10469789.
2. Goodwin RG, Din WS, Davis-Smith T, Anderson DM, Gimpel SD, et al. (1993) Molecular cloning of a ligand for the inducible T cell gene 4-1BB: a member of an emerging family of cytokines with homology to tumor necrosis factor. Eur J Immunol. 23:2631-2641.
3. Alderson MR, Smith CA, Tough TW, Davis-Smith T, Armitage RJ, et al. (1994) Molecular and biological characterization of human 4-1BB and its ligand. Eur J Immunol. 24:2219-2227.
4. Sun Y, Chen HM, Subudhi SK, Chen J, Koka R, Chen L, Fu YX. (2002) Costimulatory molecule-targeted antibody therapy of a spontaneous autoimmune disease. Nat Med. 1405-1413.
5. Agarwal A, Newell KA. (2008) The role of positive costimulatory molecules in transplantation and tolerance. Curr Opin Organ Transplant. 13:366-372
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