Anti-CD27 (Varlilumab biosimilar)

Human IgG1 monoclonal antibody (mAb) against human CD27

Anti-hCD27 mAb induces ADCC in cancer
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InvivoGen provides Anti-hCD27-hIgG1, the biosimilar of the clinical antibody varlilumab. It features:

• the variable region of varlilumab targeting the human cluster of differentiation 27 (hCD27)
• the IgG1 constant region of varlilumab mediating high effector functions

InvivoGen's Anti-hCD27-hIgG1 was generated by recombinant DNA technology, produced in Chinese hamster ovary (CHO) cells, and purified by affinity chromatography. Each lot is functionally tested by flow cytometry and cellular assays (see figures).

Varlilumab is a fully human agonist anti-CD27-hIgG1 mAb that activates the costimulatory molecule CD27 [1]. This receptor is constitutively expressed on the majority of mature T cells. In the appropriate context of T cell receptor engagement, the interaction of CD27 with its ligand CD70 (also known as CD27L) promotes T cell activation, maturation of effector capacity, and T cell memory [1-2]. This interaction became of interest to immunologists as a co-stimulatory immune checkpoint (IC) molecule and is the target of an anti-cancer drug in clinical trials [2].

 More details

Key features of the Anti-hCD27-hIgG1 

• Clinically-relevant variable region targeting human CD27 (varlilumab)
• Human IgG1 constant region for high effector functions
• Functionally validated by flow cytometry and ELISA
• The absence of bacterial contamination has been confirmed

References

1. Vitale LA, et al.,2012. Development of a human monoclonal antibody for potential therapy of CD27-expressing lymphoma and leukemia. Clin Cancer Res.;18(14):3812-21.
2. Sanborn RE, et al., 2022 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.;10(8):e005147.

Figures

Binding of Anti-hCD27-hIgG1 mAb to hCD27. Raji-Null cells were incubated for 30 minutes with 2 µg of Anti-hCD27-hIgG1 or an isotype control. Subsequently, a secondary PE-labeled antibody was added and incubated at room temperature for 30 minutes. The binding affinity was assessed using flow cytometry.

Comparison of ADCC potency for native and engineered anti-human CD27 antibody isotypes. Raji-Null cells were incubated with gradient concentrations of Anti-hCD27 or Anti-β-galactosidase (β-gal) mAbs for 1 hour. Jurkat-Lucia™ NFAT-CD16 effector cells were then co-incubated with target Raji-Null cells for 6 hours. NFAT activation, reflecting the induced ADCC response, was assessed by determining Lucia luciferase activity in the supernatant using QUANTI-Luc™ 4 Lucia/Gaussia. Percentages of the maximal response normalized to the IgG1 isotype are shown.

Specifications

Specificity: Targets cells expressing human CD27

Clonality: Monoclonal antibodies

Clone: Varlilumab (Anti-hCD27-hIgG1, kappa)

Control: Human IgG1

Source: Chinese hamster ovary (CHO) cells 

Formulation: 0.2 μm filtered solution in a sodium phosphate buffer with glycine, saccharose, and stabilizing agents.

Tested Applications: Flow cytometry, ELISA, ADCC assay

Purification: Purified by affinity chromatography with protein G

Quality control:

• The binding of Anti-hCD27 mAb to human CD27 on cells has been validated using flow cytometry.
• Isotype effector function has been validated using an ADCC cellular assay.
• The complete sequence of the antibody has been verified.
• The absence of bacterial contamination (e.g. lipoproteins and endotoxins) has been confirmed using HEK-Blue™ hTLR2 and HEK-Blue™ TLR4 cellular assays.

Contents

Anti-hCD27-hIgG1 purified monoclonal antibody is provided azide-free and lyophilized. It is available in two quantities:

• hcd27-mab1: 100 µg
• hcd27-mab1-03: 3 x 100 µg

 The product is shipped at room temperature.

 Upon receipt, store lyophilized antibody at -20 °C.

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Details

The Cluster of Differentiation CD27, a member of the TNFR family, is known as the sole receptor for CD70 (aka CD27L). The CD27–CD70 costimulatory receptor-ligand pair plays an important role in immune regulation. In concert with the T cell receptor (TCR) crosslinking, it promotes T cell activation, proliferation, survival, maturation of effector capacity, and T cell memory [1-2]. In humans, CD27 is constitutively expressed on the majority of T cells, memory B cells and plasma cells, and natural killer (NK) cells. It is also expressed on various types of hematologic cancers. In leukemia, CD27 signaling leads to the induction of different pathways, supporting stemness, tumor cell proliferation, and self-renewal [3].

The efficacy of targeting the CD27/CD70 axis with an agonistic CD27 mAbs was shown in preclinical models of lymphoma, renal cell carcinoma (RCC), breast cancer, and sarcoma [4]. A human mAb directed at CD27 named varlilumab (also CDX-1127, 1F5) has entered clinical trials. It is able to activate CD27-positive T cells, while mediating the killing of CD27-expressing tumor cells [4-5]. Also, it has successfully completed a phase I/II dose escalation and cohort expansion study (NCT02335918) in combination with nivolumab in different solid malignancies. Further phase I trials with various combinations as well as phase II trials are still ongoing in renal cell carcinoma, squamous cell carcinoma of the head and neck, ovarian and colorectal cancers, and glioblastoma [4]. 

In conclusion, the CD27/70 axis is a promising pathway for immunotherapies showing a potential clinical benefit in different hematological and solid tumors. The combination of agonistic costimulatory CD27 mAbs with currently used immune checkpoint inhibitor-targeting mAbs (e.g. anti-PD-1) is foreseen to have a synergistic effect by different favorable effects on the tumor microenvironment. Further clinical trials are needed to investigate potential combinations of immune-modulating therapies, especially at earlier stages of disease, to achieve the best possible outcome for cancer patients [4]. 

References:

1. Jacobs, J. et al., 2015. CD70: An emerging target in cancer immunotherapy. Pharmacol Ther 155, 1-10.
2. Sanborn RE, et al., 2022 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.
3. Flieswasser, T., Van den Eynde, A., Van Audenaerde, J. et al. 2022. The CD70-CD27 axis in oncology: the new kids on the block. J Exp Clin Cancer Res 41, 12. 
4. Starzer AM, Berghoff AS., 2020. New emerging targets in cancer immunotherapy: CD27 (TNFRSF7). ESMO Open. 4 (Suppl 3):e000629.
5. Vitale LA, et al.,2012. Development of a human monoclonal antibody for potential therapy of CD27-expressing lymphoma and leukemia. Clin Cancer Res. 2012 Jul 15;18(14):3812-21.