TNFRSF7/CD27

TNFRSF7/CD27 is a TNF receptor family costimulatory receptor whose CD70-dependent signaling supports T- and B-cell activation^[1]^[2]. Mechanistically, CD27 engagement provides a second signal for T-cell activation and can activate NF-κB and JNK through TRAF-associated signaling^[3]^[4]. In naïve CD8⁺ T cells, CD27-CD70 interaction promotes memory-associated gene regulatory networks through a CD27-TRAF2-SHP-1 axis^[5]. In experimental immunity models, CD27 is required for generation and long-term maintenance of T-cell immunity^[6]. Human CD27 deficiency links TNFRSF7 loss to persistent symptomatic EBV viremia, impaired T-cell-dependent antibody generation, severe EBV infection, Hodgkin lymphoma, and primary antibody deficiency^[7]^[8]. Compared with membrane-bound CD27, soluble CD27 is released after TCR/CD3 triggering and is elevated in serum from cancer patients after immunotherapy, making isoform distinction important for biomarker interpretation^[9]. For experimental applications, varlilumab is an agonist anti-CD27 antibody evaluated in advanced solid tumors and in combination with nivolumab, providing a practical tool to study CD27 pathway activation in cancer immunology^[10]^[11].

References:

[1]. Borst J, et al. CD27 and CD70 in T cell and B cell activation. Curr Opin Immunol. 2005 Jun;17(3):275-81. [Content Brief]

[2]. HintZen R Q, et al. Characterization of the human CD27 ligand, a novel member of the TNF gene family[J]. The Journal of Immunology, 1994, 152(4): 1762-1773.

[3]. Hintzen RQ, et al. Engagement of CD27 with its ligand CD70 provides a second signal for T cell activation. J Immunol. 1995 Mar 15;154(6):2612-23. [Content Brief]

[4]. Akiba H, et al. CD27, a member of the tumor necrosis factor receptor superfamily, activates NF-kappaB and stress-activated protein kinase/c-Jun N-terminal kinase via TRAF2, TRAF5, and NF-kappaB-inducing kinase. J Biol Chem. 1998 May 22;273(21):13353-8. [Content Brief]

[5]. Jaeger-Ruckstuhl CA, et al. Signaling via a CD27-TRAF2-SHP-1 axis during naive T cell activation promotes memory-associated gene regulatory networks. Immunity. 2024 Feb 13;57(2):287-302.e12. [Content Brief]

[6]. Hendriks J, et al. CD27 is required for generation and long-term maintenance of T cell immunity. Nat Immunol. 2000 Nov;1(5):433-40. [Content Brief]

[7]. van Montfrans JM, et al. CD27 deficiency is associated with combined immunodeficiency and persistent symptomatic EBV viremia. J Allergy Clin Immunol. 2012 Mar;129(3):787-793.e6. [Content Brief]

[8]. Alkhairy OK, et al. Novel mutations in TNFRSF7/CD27: Clinical, immunologic, and genetic characterization of human CD27 deficiency. J Allergy Clin Immunol. 2015 Sep;136(3):703-712.e10. [Content Brief]

[9]. Hintzen R Q, et al. A soluble form of the human T cell differentiation antigen CD27 is released after triggering of the TCR/CD3 complex[J]. The Journal of Immunology, 1991, 147(1): 29-35.

[10]. Burris HA, et al. Safety and Activity of Varlilumab, a Novel and First-in-Class Agonist Anti-CD27 Antibody, in Patients With Advanced Solid Tumors. J Clin Oncol. 2017 Jun 20;35(18):2028-2036. [Content Brief]

[11]. Sanborn RE, et al. Safety, tolerability and efficacy of agonist anti-CD27 antibody (varlilumab) administered in combination with anti-PD-1 (nivolumab) in advanced solid tumors. J Immunother Cancer. 2022 Aug;10(8):e005147. [Content Brief]

TNFRSF7/CD27 Agonist (1)

TNFRSF7/CD27 Related Products (2):

Cat. No.	Product Name	Effect	Purity

HY-159886

MG-C-30	Agonist
MG-C-30 is an orally active agonist for CD27 with an EC₅₀ of 0.84 μM. MG-C-30 activates NK cells and T cell co-stimulatory signals, and enhances immune response. MG-C-30 exhibits antitumor efficacy in mouse EG7-OVA model.

HY-P991661

AMG-172 Antibody
AMG-172 Antibody is an anti-CD27L antibody. AMG-172 Antibody can be used for synthesis of ADC AMG-172 (HY-185483).

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