CD137 is a member of the tumor necrosis factor (TNF) receptor family. Its alternative names are tumor necrosis factor receptor superfamily member 9 (TNFRSF9), 4-1BB and induced by lymphocyte activation (ILA). It is currently of interest to immunologists as a co-stimulatory immune checkpoint molecule.
CD137 can be expressed by activated T cells, but to a larger extent on CD8 than on CD4T cells. In addition, CD137 expression is found on dendritic cells, B cells, follicular dendritic cells, natural killer cells, granulocytes and cells of blood vessel walls at sites of inflammation.
The best characterized activity of CD137 is its costimulatory activity for activated T cells. Crosslinking of CD137 enhances T cell proliferation, IL-2 secretion, survival and cytolytic activity. Further, it can enhance immune activity to eliminate tumors in mice.
Utomilumab (PF-05082566) targets this receptor to stimulate a more intense immune system attack on cancers. It is a fully human IgG2 monoclonal antibody. It is in early clinical trials. As of June 2016[update] 5 clinical trials are active.
Schwarz H, Tuckwell J, Lotz M (1993). "A receptor induced by lymphocyte activation (ILA): a new member of the human nerve-growth-factor/tumor-necrosis-factor receptor family". Gene. 134 (2): 295–8. doi:10.1016/0378-1119(93)90110-O. PMID8262389.
Sica G, Chen L (2000). "Biochemical and immunological characteristics of 4-1BB (CD137) receptor and ligand and potential applications in cancer therapy". Arch. Immunol. Ther. Exp. (Warsz.). 47 (5): 275–9. PMID10604232.
Zhou Z, Kim S, Hurtado J, Lee ZH, Kim KK, Pollok KE, Kwon BS (1995). "Characterization of human homologue of 4-1BB and its ligand". Immunol. Lett. 45 (1–2): 67–73. doi:10.1016/0165-2478(94)00227-I. PMID7622190.
Alderson MR, Smith CA, Tough TW, Davis-Smith T, Armitage RJ, Falk B, Roux E, Baker E, Sutherland GR, Din WS (1994). "Molecular and biological characterization of human 4-1BB and its ligand". Eur. J. Immunol. 24 (9): 2219–27. doi:10.1002/eji.1830240943. PMID8088337.
Schwarz H, Tuckwell J, Lotz M (1994). "A receptor induced by lymphocyte activation (ILA): a new member of the human nerve-growth-factor/tumor-necrosis-factor receptor family". Gene. 134 (2): 295–8. doi:10.1016/0378-1119(93)90110-O. PMID8262389.
Schwarz H, Blanco FJ, von Kempis J, Valbracht J, Lotz M (1996). "ILA, a member of the human nerve growth factor/tumor necrosis factor receptor family, regulates T-lymphocyte proliferation and survival". Blood. 87 (7): 2839–45. PMID8639902.
Loo DT, Chalupny NJ, Bajorath J, Shuford WW, Mittler RS, Aruffo A (1997). "Analysis of 4-1BBL and laminin binding to murine 4-1BB, a member of the tumor necrosis factor receptor superfamily, and comparison with human 4-1BB". J. Biol. Chem. 272 (10): 6448–56. doi:10.1074/jbc.272.10.6448. PMID9045669.
Schwarz H, Arden K, Lotz M (1997). "CD137, a member of the tumor necrosis factor receptor family, is located on chromosome 1p36, in a cluster of related genes, and colocalizes with several malignancies". Biochem. Biophys. Res. Commun. 235 (3): 699–703. doi:10.1006/bbrc.1997.6870. PMID9207223.
Jang IK, Lee ZH, Kim YJ, Kim SH, Kwon BS (1998). "Human 4-1BB (CD137) signals are mediated by TRAF2 and activate nuclear factor-kappa B". Biochem. Biophys. Res. Commun. 242 (3): 613–20. doi:10.1006/bbrc.1997.8016. PMID9464265.
Langstein J, Michel J, Schwarz H (1999). "CD137 induces proliferation and endomitosis in monocytes". Blood. 94 (9): 3161–8. PMID10556203.
Jang LK, Lee ZH, Kim HH, Hill JM, Kim JD, Kwon BS (2002). "A novel leucine-rich repeat protein (LRR-1): potential involvement in 4-1BB-mediated signal transduction". Mol. Cells. 12 (3): 304–12. PMID11804328.
Wilcox RA, Chapoval AI, Gorski KS, Otsuji M, Shin T, Flies DB, Tamada K, Mittler RS, Tsuchiya H, Pardoll DM, Chen L (2002). "Cutting edge: Expression of functional CD137 receptor by dendritic cells". J. Immunol. 168 (9): 4262–7. doi:10.4049/jimmunol.168.9.4262. PMID11970964.
Shulzhenko N, Morgun A, Chinellato AP, Rampim GF, Diniz RV, Almeida DR, Gerbase-DeLima M (2002). "CD27 but not CD70 and 4-1BB intragraft gene expression is a risk factor for acute cardiac allograft rejection in humans". Transplant. Proc. 34 (2): 474–5. doi:10.1016/S0041-1345(02)02600-3. PMID12009595.
Pauly S, Broll K, Wittmann M, Giegerich G, Schwarz H (2002). "CD137 is expressed by follicular dendritic cells and costimulates B lymphocyte activation in germinal centers". J. Leukoc. Biol. 72 (1): 35–42. PMID12101260.