Anti-CD27

Smilax zeylanica Linn is explored as a natural solution to inhibit the CD27/CD70 interaction crucial in T and B cell responses. This plant-based approach offers a cost-effective and promising drug candidate for overcoming challenges associated with anti-CD27 antibodies. The plants were macerated in an ethanol solution, and the cytotoxicity of crude extracts was determined using the MTT assay on Vero cell lines. Preliminary antiviral activity against the lentivirus plasmid was analyzed using plaque reduction assays for both ethanol and methanol fractions of the ethanol extract...

INTRODUCTION: T cell expressed CD27 provides costimulation upon binding to inducible membrane expressed trimeric CD70 and is required for protective CD8 T cell responses. CD27 agonists could therefore be used to bolster cellular vaccines and anti-tumour immune responses. To date, clinical development of CD27 agonists has focussed on anti-CD27 antibodies with little attention given to alternative approaches. METHODS: Here, we describe the generation and activity of soluble variants of CD70 that form either trimeric (t) or dimer-of-trimer proteins and conduct side-by-side comparisons with an agonist anti-CD27 antibody...

BACKGROUND: Central nervous system (CNS) WHO grade 2 low-grade glioma (LGG) patients are at high risk for recurrence and with unfavorable long-term prognosis due to the treatment resistance and malignant transformation to high-grade glioma. Considering the relatively intact systemic immunity and slow-growing nature, immunotherapy may offer an effective treatment option for LGG patients. METHODS: We conducted a prospective, randomized pilot study to evaluate the safety and immunological response of the multipeptide IMA950 vaccine with agonistic anti-CD27 antibody, varlilumab, in CNS WHO grade 2 LGG patients...

INTRODUCTION: Aplasia and hematological malignancies are treated with platelet transfusions, which can have major immunomodulatory effects. Platelet concentrates (PCs) contain many immunomodulatory elements, including the platelets themselves, residual leukocytes, extracellular vesicles, such as microparticles (MPs), cytokines and other soluble elements. Two of these components, MPs and a soluble form of CD27 (sCD27), have been shown to play a particularly important role in immune system modulation...

BACKGROUND: Immune checkpoint inhibitors (ICI) have radically changed cancer therapy, but most patients with cancer are unresponsive or relapse after treatment. MK-5890 is a CD27 agonist antibody intended to complement ICI therapy. CD27 is a member of the tumor necrosis factor receptor superfamily that plays a critical role in promoting responses of T cells, B cells and NK cells. METHODS: Anti-CD27 antibodies were generated and selected for agonist activity using NF-кB luciferase reporter assays...

BACKGROUND: Phase 1/2 dose-escalation and expansion study evaluating varlilumab, a fully human agonist anti-CD27 mAb, with nivolumab in anti-PD-1/L1 naïve, refractory solid tumors. METHODS: Phase 1 evaluated the safety of varlilumab (0.1-10 mg/kg) with nivolumab (3 mg/kg) administered once every 2 weeks. Phase 2 evaluated varlilumab regimens (3 mg/kg once every 2 weeks, 3 mg/kg once every 12 weeks, and 0.3 mg/kg once every 4 weeks) with nivolumab 240 mg once every 2 weeks in tumor-specific cohorts...

CD27/CD70 costimulation enhances T-cell survival, memory formation and Th1-cell differentiation and effector function. In addition to promoting Th1 responses, CD27 signaling has been shown to exert a negative regulatory role on IL-17 production, resulting in increased sensitivity of CD27 KO mice to EAE. By inducing EAE in full CD27 KO mice, and in a novel, T-cell specific CD27 KO mouse strain (CD4-Cre x CD27flox/flox ), we demonstrate herein that CD27 engagement by its natural ligand (CD70) suppresses IL-17 production in a cell autonomous fashion...

BACKGROUND: The etiopathogenesis of MF remains obscure. CD27 is a member of the tumor necrosis factor receptor superfamily (TNFRS) that regulates lymphocyte function4. Expression of CD27 protein and mRNA has been reported in B-cell lymphomas5 and adult T-cell leukemia/lymphoma6. In this study, we examined the expression of CD27 in the skin of MF patients by real time PCR. The amount of CD27 was measured in MF patients and healthy controls. METHODS: A total of 98 skin biopsies were analyzed: 12 obtained from healthy donors and 86 obtained Cryostatic sections OCT-embedded affected by MF...

Isolating cells based on their secreted proteins remain a challenge. The authors demonstrate a capacity for high throughput single-cell protein secretion analysis and isolation based on heterofunctional particles combined with fluorescence activated cell sorting (FACS). The workflow shows that antibody secreting cells (ASCs) specific for the H1 protein from influenza virus can be isolated from B cells. The workflow consists of incubating anti-CD27 particles with the ASCs, capturing locally secreted immunoglobulins with Protein G on the particles, and identifying immunoglobulins specific to H1 via fluorescent labeled antigens followed by FACS to enrich antigen-specific ASCs...

This mini-review is a short overview of different therapeutical strategies targeting B cells in systemic autoimmune rheumatic diseases, mainly: rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and primary Sjogren Syndrome (pSS). Many strategies and their rationale are discussed in this review: B cells' depletion (anti-CD20, anti-CD22), long-lived plasma cells depletion (anti-CD19, anti-CD27, anti-CD38 and anti-CD138), changing activation of B cells (anti-BAFF) and inhibiting proteasomes in plasma cells (bortezomib)...

CD27, a costimulatory molecule on T cells, induces intracellular signals mediating cellular activation, proliferation, effector function, and cell survival on binding to its ligand, CD70. Varlilumab, a novel, first-in-class, agonist immunoglobulin G1 anti-CD27 antibody, mediates antitumor immunity and direct killing of CD27+ tumor cells in animal models. This first-in-human, dose-escalation, and expansion study evaluated varlilumab in patients with hematologic malignancies. Primary objectives were to assess safety and the maximum tolerated and optimal biologic doses of varlilumab...

PURPOSE: Transient hypogammaglobulinemia of infancy (THI) is a common immunodeficiency, but definitive diagnosis can only be made retrospectively. While the pathogenesis is still unknown, abnormalities have been reported in the B cell compartment. In this study, we analysed the B cell subsets of patients with an initial THI diagnosis (n = 20) and compared them with those of healthy age-matched Turkish children (n = 72). METHODS: Flow cytometric analyses of the B subsets were performed by staining with anti-CD27-PE, anti-CD19-PerCP, anti-IgD-FITC and anti-IgM-APC antibodies...

Purpose: PD-1 checkpoint blockade has revolutionized the field of cancer immunotherapy, yet the frequency of responding patients is limited by inadequate T-cell priming secondary to a paucity of activatory dendritic cells (DC). DC signals can be bypassed by CD27 agonists, and we therefore investigated if the effectiveness of anti-PD-1/L1 could be improved by combining with agonist anti-CD27 monoclonal antibodies (mAb). Experimental Design: The efficacy of PD-1/L1 blockade or agonist anti-CD27 mAb was compared with a dual-therapy approach in multiple tumor models...

Monoclonal antibodies (mAbs) can destroy tumors by recruiting effectors such as myeloid cells, or targeting immunomodulatory receptors to promote cytotoxic T cell responses. Here, we examined the therapeutic potential of combining a direct tumor-targeting mAb, anti-CD20, with an extended panel of immunomodulatory mAbs. Only the anti-CD27/CD20 combination provided cures. This was apparent in multiple lymphoma models, including huCD27 transgenic mice using the anti-huCD27, varlilumab. Detailed mechanistic analysis using single-cell RNA sequencing demonstrated that anti-CD27 stimulated CD8+ T and natural killer cells to release myeloid chemo-attractants and interferon gamma, to elicit myeloid infiltration and macrophage activation...

CD27, a member of the TNFR superfamily, is constitutively expressed in most T cells and plays crucial roles in T cell effector functions. The costimulation and antitumor activity of CD27 agonistic Abs have been well documented in mouse models. Clinical testing of a human IgG1 anti-CD27 Ab, varlilumab (clone 1F5), is ongoing in cancer patients. In this study, we set out to further understand CD27 as an immunomodulatory target and to address the mechanism of antitumor efficacy using different IgG isotypes of 1F5 in human CD27 -transgenic mice...

BACKGROUND: Multiple myeloma (MM) is an incurable disease characterized by clonal plasma cell (PC) proliferation within the bone marrow (BM). Next-generation flow cytometry has become the reference tool to follow minimal residual disease (MRD). We developed a new simpler and cheaper flow cytometry method to analyze bone marrow samples in patients with MM. METHODS: To identify and characterize abnormal PCs, we designed a simple panel composed of anti-CD38, antikappa, and antilambda light chain antibodies, combined with two antibody pools with the same fluorophore (anti-CD19 and anti-CD27 for the negative pool and anti-CD56, anti-CD117, and anti-CD200 antibodies for the positive pool)...

CD27 is a T-cell and B-cell co-stimulatory glycoprotein of the tumor necrosis factor (TNF) receptor superfamily that is dependent on the availability of the TNF-like ligand CD70. Therapeutic approaches to treating autoimmune diseases and cancers with antagonistic and agonistic anti-CD27 monoclonal antibodies (mAbs), respectively, have recently been developed. Mouse anti-human CD27 mAb 2177 shows potency in neutralizing CD70-induced signaling; however, it does not block the binding of soluble CD70. To provide insight into the mechanism of action of the mAb, the crystal structure of the CD27 extracellular domain in complex with the Fab fragment of mAb 2177 was determined at 1...

Purpose CD27, a costimulatory molecule on T cells, induces intracellular signals that mediate cellular activation, proliferation, effector function, and cell survival upon binding to its ligand, CD70. Varlilumab is a novel, first-in-class, agonist CD27 antibody that stimulates the CD27 pathway, which results in T-cell activation and antitumor activity in tumor models. This first-in-human, dose-escalation and expansion study evaluated the safety, pharmacology, and activity of varlilumab in patients with advanced solid tumors...

CD27 is a T and B cell co-stimulatory protein of the TNF receptor superfamily dependent on the availability of the TNF-like ligand CD70. Two anti-CD27 neutralizing monoclonal antibodies were obtained from mouse hybridoma and subsequently humanized and optimized for binding the target. The two antibodies are similar in terms of their CD27-binding affinity and ability to block NF-κB signaling, however their clearance rates in monkeys are very different. The pharmacokinetics profiles could be epitope dependent...

T and natural killer (NK) lymphocytes are considered the main effector players in the immune response against tumors. Full activation of T and NK lymphocytes requires the coordinated participation of several surface receptors that meet their cognate ligands through structured transient cell-to-cell interactions known as immune synapses. In the case of T cells, the main route of stimulation is driven by antigens as recognized in the form of short polypeptides associated with major histocompatibility complex (MHC) antigen-presenting molecules...