4-1BB/TNFRSF9/CD137 Antibody (145501) [Janelia Fluor® 669]

Sold under license from the Howard Hughes Medical Institute, Janelia Research Campus.

4-1BB, also called CD137 and tumor necrosis factor receptor superfamily member 9 (TNFRSF9), is a type I surface glycoprotein expressed on activated T cell and natural killer (NK) cells (1,2). Human 4-1BB protein is 255 amino acids (aa) in length with a theoretical molecular weight of 28 kDa. It contains an extracellular domain, a helical transmembrane domain, and a cytoplasmic/intracellular domain (3). 4-1BB/TNFRSF9/CD137 is a costimulatory receptor that binds the ligand 4-1BBL/CD137L which is primarily expressed on antigen presenting cells (APCs) such as dendritic cells (DCs), macrophages, and B cells (1,2,4,5). The 4-1BB receptor-ligand interaction results in recruitment of TNFR-associated factor (TRAF) family adaptor proteins to 4-1BB's cytoplasmic domain (1,2,4,5). TRAF1, TRAF2, and TRAF3 are found in various homodimer and/or heterodimer configurations. Their recruitment to 4-1BB/CD137 initiates signalosome formation as well as activation of the nuclear factor-kappa B (NF-kappaB) and mitogen-activated protein kinase (MAPK) signaling cascade (1,4,5). 4-1BB/TNFRSF9/CD137 stimulation leads to increased cellular cytotoxic activity and pro-inflammatory cytokine production (1,2,4). Given its role in immune cell activation, 4-1BB has become a promising target for cancer immunotherapy (1,2,4). Current approaches to target 4-1BB include agonistic monoclonal and bispecific anti-4-1BB antibodies and well as utilizing the cytoplasmic domain of 4-1BB in generating chimeric antigen receptors (CARs) (1,2,4). 4-1BB agonists in clinical trials include Urelumab and Utolimumab. Utolimumab also has ligand blocking properties whereas Urelumab does not (1,2,4). Anti-4-1BB monoclonal antibodies are being tested as monotherapy as well as combination therapy with either other immunostimulatory monoclonal antibodies or with checkpoint blockade antibodies like anti-PD-1 (1,2,4).

References

1. Etxeberria, I., Glez-Vaz, J., Teijeira, A., & Melero, I. (2020). New emerging targets in cancer immunotherapy: CD137/4-1BB costimulatory axis. ESMO open, 4(Suppl 3), e000733. https://doi.org/10.1136/esmoopen-2020-000733

2. Chester, C., Sanmamed, M. F., Wang, J., & Melero, I. (2018). Immunotherapy targeting 4-1BB: mechanistic rationale, clinical results, and future strategies. Blood, 131(1), 49-57. https://doi.org/10.1182/blood-2017-06-741041

3. Uniport (Q07011)

4. Chester, C., Ambulkar, S., & Kohrt, H. E. (2016). 4-1BB agonism: adding the accelerator to cancer immunotherapy. Cancer Immunology, Immunotherapy: CII, 65(10), 1243-1248. https://doi.org/10.1007/s00262-016-1829-2

5. Zapata, J. M., Perez-Chacon, G., Carr-Baena, P., Martinez-Forero, I., Azpilikueta, A., Otano, I., & Melero, I. (2018). CD137 (4-1BB) signalosome: complexity is a matter of TRAFs. Frontiers in Immunology, 9, 2618. https://doi.org/10.3389/fimmu.2018.02618

This product is for research use only and is not approved for use in humans or in clinical diagnosis. Primary Antibodies are guaranteed for 1 year from date of receipt.

Array FAB838JF669

• 4-1BB/TNFRSF9/CD137 Antibodies
• 4-1BB/TNFRSF9/CD137 ELISA Kit
• 4-1BB/TNFRSF9/CD137 Proteins
• 4-1BB/TNFRSF9/CD137 ELISAs
• 4-1BB/TNFRSF9/CD137 Proteins and Enzymes