Varlilumab |
Catalog No.GC64839
One-Click Copy Product Info
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Varlilumab is a fully human IgG1κ agonistic anti-CD27 monoclonal antibody that activates CD8⁺ T cell proliferation, survival, and cytotoxicity, enhances NK cell activity, and exerts Fc-dependent effector functions.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1393344-72-3
Sample solution is provided at 25 µL, 10mM.
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Varlilumab is a fully human IgG1κ agonistic anti-CD27 monoclonal antibody that activates CD8⁺ T cell proliferation, survival, and cytotoxicity, enhances NK cell activity, and exerts Fc-dependent effector functions. Varlilumab can be used in research related to advanced solid tumors and hematological malignancies[1-4].
In vitro, Varlilumab (10μg/ml) was incubated with anti-CD3 antibody (1μg/ml) and Pan T cells for 72h. Varlilumab promoted the activation and proliferation of memory CD4⁺ and CD8⁺ T cells, upregulated the expression of costimulatory molecules such as 4-1BB, OX40, GITR, and ICOS as well as PD-1, and induced the secretion of IFNγ, IL-2, TNFα, IL-13, IL-5, GM-CSF, and CD40L[5].
In vivo, Varlilumab (100μg; once daily) was intraperitoneally injected into BCL1 lymphoma-bearing BALB/c mice (human CD27 transgenic) on days 5-8 after BCL1 tumor inoculation. Varlilumab monotherapy prolonged the survival of tumor-bearing mice, enhanced the infiltration of monocytes and neutrophils into the spleen, and upregulated FcγRIV expression on myeloid cells[6]. Varlilumab (200μg; i.p.; days 4, 6, 8, 10, 12) combined with anti-PD-L1 monoclonal antibody (100μg; i.p.; days 4, 6, 8) was administered to BCL1 lymphoma-bearing mice (human CD27 transgenic). The combination of Varlilumab and anti-PD-L1 antibody significantly improved the survival rate of mice bearing BCL1 lymphoma[7].
References:
[1] Leitner J, Egerer R, Waidhofer-Söllner P, et al. FcγR requirements and costimulatory capacity of Urelumab, Utomilumab, and Varlilumab. Front Immunol. 2023 Jul 27;14:1208631.
[2] Ansell SM, Flinn I, Taylor MH, et al. Safety and activity of varlilumab, a novel and first-in-class agonist anti-CD27 antibody, for hematologic malignancies. Blood Adv. 2020 May 12;4(9):1917-1926.
[3] Nguyen KD, Kajiura H, Kamiya R, et al. Production and N-glycan engineering of Varlilumab in Nicotiana benthamiana. Front Plant Sci. 2023 Aug 8;14:1215580.
[4] Sanborn RE, Pishvaian MJ, Callahan MK, 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.
[5] Ramakrishna V, Sundarapandiyan K, Zhao B, et al. Characterization of the human T cell response to in vitro CD27 costimulation with varlilumab. J Immunother Cancer. 2015 Aug 18;3:37.
[6] Turaj AH, Hussain K, Cox KL, et al. Antibody Tumor Targeting Is Enhanced by CD27 Agonists through Myeloid Recruitment. Cancer Cell. 2017 Dec 11;32(6):777-791.e6.
[7] Buchan SL, Fallatah M, Thirdborough SM, et al. PD-1 Blockade and CD27 Stimulation Activate Distinct Transcriptional Programs That Synergize for CD8+ T-Cell-Driven Antitumor Immunity. Clin Cancer Res. 2018 May 15;24(10):2383-2394.
| Cell experiment [1]: | |
Cell lines | Human peripheral blood pan T cells |
Preparation Method | T cell subsets were cultured in RPMI 1640 medium supplemented with 10% heat-inactivated fetal bovine serum, L-glutamine, penicillin and streptomycin at 37°C in a humidified 5% CO₂ incubator. Multi-well plates were dry-coated with suboptimal plate-bound anti-CD3 antibody (OKT3; 1μg/ml) combined with Varlilumab (10μg/ml) or isotype-matched control human IgG1 (10μg/ml; plate coating is required for Varlilumab to exert costimulatory effect via effective cross-linking); for kinetic experiments, T cells were pre-stimulated with OKT3 alone for 46h, then transferred to Varlilumab+OKT3-coated plates for 4h costimulation. |
Reaction Conditions | 10μg/ml; 72h |
Applications | Varlilumab-mediated CD27 costimulation required concurrent continuous TCR signaling, as pre-activated T cells failed to produce cytokines upon Varlilumab treatment alone. Memory CD4⁺ and CD8⁺ T cells were specifically activated with a bias toward CD8⁺ T lymphocyte proliferation, and activated T cells showed upregulated surface expression of costimulatory (4-1BB, OX40, GITR, ICOS) and coinhibitory (PD-1) molecules. Varlilumab costimulation did not activate purified Tregs, with minimal driving effects on their cytokine secretion and proliferation. |
| Animal experiment [2]: | |
Animal models | Human CD27 transgenic (hCD27-Tg) BALB/c mice bearing BCL1 lymphoma |
Preparation Method | hCD27-Tg mice were challenged intravenously with 1×10⁷ BCL1 tumor cells. In a sub-optimized setting where Varlilumab monotherapy was set to show no efficacy, mice were intraperitoneally injected with 200μg Varlilumab on days 4, 6, 8, 10 and 12 post-tumor challenge, alone or in combination with 100μg anti-PD-L1 monoclonal antibody on days 4, 6 and 8. Tumor-bearing mice were monitored for survival to the humane endpoint. |
Dosage form | 200μg/mouse; i.p.; days 4, 6, 8, 10, 12 post-tumor challenge |
Applications | Varlilumab monotherapy had little impact on tumor growth in this sub-optimized BCL1 model, whereas combined treatment with PD-L1 blockade conferred significant long-term protection, with over half of the mice surviving longer than 80 days. |
References: | |
| Cas No. | 1393344-72-3 | SDF | |
| Formula | M.Wt | ||
| Solubility | Storage | Store at -80°C | |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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Purity: >96.00%
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- SDS (Safety Data Sheet)
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Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)