TNFRSF9/4-1BB/CD137

TNFRSF9/4-1BB/CD137 is a TNF receptor superfamily member that provides costimulatory signals for activated T cells and mediates growth and survival signals for T cells^[1]. Mechanistically, 4-1BB functions with TCR/CD3 stimulation and activates JNK signaling in T cells^[2]. This pathway supports activated CD8⁺ T-cell costimulation, cytotoxic responses, and memory T-cell formation, while CD137 signaling can also activate NK cells and dendritic cells^[3]. In monocytes, CD137 induces IL-8 and TNF-α production, inhibits IL-10 expression, and links CD137 biology to innate immune activation^[4]. In disease models, TNFRSF9 variation affects type 1 diabetes susceptibility, and 4-1BB costimulation changes IL-2 production and T-cell proliferation in NOD congenic mice^[1]. In lichen planus, CXCL13⁺CD8⁺ T cells express TNFRSF9, which enhances cytotoxic responses in skin^[5]. Compared with membrane-bound CD137, soluble CD137 is generated by alternative splicing, released by activated lymphocytes, and detected at increased levels in rheumatoid arthritis sera^[6]. For research applications, agonistic anti-4-1BB antibody directly stimulates peptide-specific CD8⁺ T cells and supports long-lasting CD8 memory in vaccination models^[7].

References:

[1]. Cannons JL, et al. Genetic and functional association of the immune signaling molecule 4-1BB (CD137/TNFRSF9) with type 1 diabetes. J Autoimmun. 2005 Aug;25(1):13-20. [Content Brief]

[2]. Kim HH, et al. Activation of c-jun N-terminal kinase by 4-1BB (CD137), a T cell co-stimulatory molecule. Mol Cells. 2000 Jun 30;10(3):247-52. [Content Brief]

[3]. Hashimoto K. CD137 as an Attractive T Cell Co-Stimulatory Target in the TNFRSF for Immuno-Oncology Drug Development. Cancers (Basel). 2021 May 11;13(10):2288. doi: 10.3390/cancers13102288. PMID: 34064598; PMCID: PMC8150789. et al. CD137 as an Attractive T Cell Co-Stimulatory Target in the TNFRSF for Immuno-Oncology Drug Development. Cancers (Basel). 2021 May 11;13(10):2288. [Content Brief]

[4]. Kienzle G, et al. CD137 (ILA/4-1BB), expressed by primary human monocytes, induces monocyte activation and apoptosis of B lymphocytes. Int Immunol. 2000 Jan;12(1):73-82. [Content Brief]

[5]. Jiang R, et al. Single-cell and spatial profiling reveal cDC2A-CXCL13⁺CD8⁺ T-epithelial cell crosstalk and cytotoxicity through TNFRSF9 in cutaneous and mucosal lichen planus. Nat Commun. 2026 Mar 14;17(1):3962. [Content Brief]

[6]. Michel J, et al. A soluble form of CD137 (ILA/4-1BB), a member of the TNF receptor family, is released by activated lymphocytes and is detectable in sera of patients with rheumatoid arthritis. Eur J Immunol. 1998 Jan;28(1):290-5. [Content Brief]

[7]. Myers L, et al. Combined CD137 (4-1BB) and adjuvant therapy generates a developing pool of peptide-specific CD8 memory T cells. Int Immunol. 2006 Feb;18(2):325-33. [Content Brief]

TNFRSF9/4-1BB/CD137 Inhibitors (3)

TNFRSF9/4-1BB/CD137 Related Products (3):

By Type:	Pan (2)

Cat. No.	Product Name	Effect	Purity

HY-P99056

Utomilumab	Inhibitor	99.33%
Utomilumab (PF 05082566) is a fully human IgG2 agonist monoclonal antibody that selectively binds to 4-1BB/CD137. Utomilumab can be used in the research of tumors such as follicular and other CD20⁺ non-Hodgkin lymphomas.

HY-P99605

Cinrebafusp alfa	Inhibitor	98.53%
Cinrebafusp alfa (PRS 343) is a high affinity CD137/HER2 bispecfic anticalin-based drug. Cinrebafusp alfa binds to recombinant human HER2 (K_d=0.3 nM) and human monomeric CD137 (4-1BB; K_d=5 nM). Cinrebafusp alfa facilitates T-cell costimulation by tumor-localized, HER2-dependent 4-1BB clustering and activation, further enhancing T-cell receptor-mediated activity and leading to tumor destruction. Cinrebafusp alfa has the potential for HER2+ solid tumors research.

HY-P99572

Tecaginlimab	Inhibitor	99.00%
Tecaginlimab (BNT-312) is a Fc-inert bispecific antibody for dual targeting and conditional stimulation of CD40 and 4-1BB. Tecaginlimab can enhance priming and reactivation of tumor-specific immunity.

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