Profiling of donor-specific immune effector signatures in response to rituximab in a human whole blood loop assay using blood from CLL patients

Eltahir, Mohamed; Fletcher, Erika; Dynesius, Linn; Jarblad, Justyna Leja; Lord, Martin; Laurén, Ida; Zekarias, Mikaela; Yu, Xiaojie; Cragg, Mark S.; Hammarström, Clara; Levedahl, Kerstin Hamberg; Höglund, Martin; Ullenhag, Gustav; Mattsson, Mattias; Mangsbo, Sara M.

doi:10.1016/j.intimp.2020.107226

Cited by 6 publications

(7 citation statements)

References 47 publications

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“… 54 , 55 Rituximab, a chimeric anti-CD20 mAb, is widely used to treat hematological malignancies, including CD20-positive diffuse large B-cell lymphoma and 56 and chronic lymphocytic leukemia. 57 Severe CRS has occurred in patients receiving rituximab, who had severe dyspnea, fever and blood pressure changes. Cytokine of TNF-α, IL-6, and IFN-γ reached the peak at 2 h after rituximab infusion in chronic lymphocytic leukemia (CLL) patients.…”

Section: Crs In Iatrogenic Diseasesmentioning

confidence: 99%

Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy

Shao

Zhang

et al. 2021

Sig Transduct Target Ther

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Cytokine release syndrome (CRS) embodies a mixture of clinical manifestations, including elevated circulating cytokine levels, acute systemic inflammatory symptoms and secondary organ dysfunction, which was first described in the context of acute graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation and was later observed in pandemics of influenza, SARS-CoV and COVID-19, immunotherapy of tumor, after chimeric antigen receptor T (CAR-T) therapy, and in monogenic disorders and autoimmune diseases. Particularly, severe CRS is a very significant and life-threatening complication, which is clinically characterized by persistent high fever, hyperinflammation, and severe organ dysfunction. However, CRS is a double-edged sword, which may be both helpful in controlling tumors/viruses/infections and harmful to the host. Although a high incidence and high levels of cytokines are features of CRS, the detailed kinetics and specific mechanisms of CRS in human diseases and intervention therapy remain unclear. In the present review, we have summarized the most recent advances related to the clinical features and management of CRS as well as cutting-edge technologies to elucidate the mechanisms of CRS. Considering that CRS is the major adverse event in human diseases and intervention therapy, our review delineates the characteristics, kinetics, signaling pathways, and potential mechanisms of CRS, which shows its clinical relevance for achieving both favorable efficacy and low toxicity.

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Section: Crs In Iatrogenic Diseasesmentioning

confidence: 99%

Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy

Shao

Zhang

et al. 2021

Sig Transduct Target Ther

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“…The WBLA has previously been shown to provide information on the interaction between monoclonal antibodies and the FcγRIIIA on NK cells, resulting in NK cell activation and cytokine release. [ 23 ] Using this system, two distinct profiles were noted based on antibody subclass, with NK cell activation taking place with IgG1 subclass but not IgG2 (Figure S3, Supporting Information). Although the SPR analyses indicated a retained FcγRIIIA binding for the BiTag of IgG1 subclass, Bi1‐CP (Table 4), the parental CP‐1 induced NK cell cytokine production in the WBLA, while the BiTag counterpart Bi1‐CP did not (Figure 2B).…”

Section: Resultsmentioning

confidence: 99%

“…Next, a WBLA [17,21,23] was used to study the BiTag antibodies interaction with Fc𝛾RIIIA on natural killer (NK) cells using whole human blood. The WBLA has previously been shown to provide information on the interaction between monoclonal antibodies and the Fc𝛾RIIIA on NK cells, resulting in NK cell activation and cytokine release.…”

Section: Adac Design and Characterizationmentioning

confidence: 99%

An Adaptable Antibody‐Based Platform for Flexible Synthetic Peptide Delivery Built on Agonistic CD40 Antibodies

Eltahir

Lord

Chourlia

et al. 2022

Advanced Therapeutics

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The agonistic potentials of therapeutic anti‐CD40 antibodies have been profiled in relation to antibody isotype and epitope specificity. Still, clinical impact relies on a well‐balanced clinical efficacy versus target‐mediated toxicity. As CD40‐mediated immune activation must rely on a combination of stimulation of antigen‐presenting cells (APCs) alongside antigen presentation, for efficient T cell priming, alternative approaches to improve the therapeutic outcome of CD40‐targeting strategies should focus on providing optimal antigen presentation together with CD40 stimulation. Herein, a bispecific antibody targeting CD40 as a means to deliver cargo (i.e., synthetic peptides) into APCs through a non‐covalent, high‐affinity interaction between the antibody and the cargo peptide, further referred to as the Adaptable Drug Affinity Conjugate (ADAC) technology, has been developed. The ADAC platform demonstrated a target‐specific CD4+ and CD8+ T cell expansion in vitro and significantly improved peptide‐specific CD8+ T cell proliferation in vivo. In addition, the strategy dramatically improved the in vitro and in vivo half‐life of the synthetic peptides. Future applications of ADAC involve pandemic preparedness to viral genetic drift as well as neoepitope vaccination strategies where the bispecific antibody is an off‐the‐shelf product, and the peptide antigen is synthesized based on next‐generation sequencing data mining.

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“…When a pair of antibodies binds to a target protein, the probes are brought into proximity, hybridized, and extended by a proximity-dependent DNA polymerization event, followed by quantification using real-time polymerase chain reaction (qPCR) [6]. Today more than 500 publications have reported use of this method in biomarker studies, including more than 90 cancer biomarker publications [7][8][9][10][11][12]. One of the most widely used PEA panels in cancer research is the 92-protein immuno-oncology (I-O) panel from Olink ® proteomics (Uppsala, Sweden) [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

“…Today more than 500 publications have reported use of this method in biomarker studies, including more than 90 cancer biomarker publications [7][8][9][10][11][12]. One of the most widely used PEA panels in cancer research is the 92-protein immuno-oncology (I-O) panel from Olink ® proteomics (Uppsala, Sweden) [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Determination of temporal reproducibility and variability of cancer biomarkers in serum and EDTA plasma samples using a proximity extension assay

Christensen

Maag²,

Madsen³

et al. 2022

Clin Proteom

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Background Proximity extension assay (PEA) is a novel antibody-based proteomic technology. Sparse data have been published concerning the matrix effect of serum vs. ethylenediamine tetraacetic acid (EDTA) plasma and the reproducibility of results obtained using PEA technology. Methods We analyzed samples with the PEA-based 92-plex Olink® immuno-oncology (I-O) assay. To estimate the matrix effect, we analyzed paired serum and EDTA plasma samples from 12 patients with biliary tract cancer. To evaluate the reproducibility, we used data from 7 studies, where 6–8 serum samples from patients with pancreatic cancer were used as bridging samples on 3 versions of the panel over a 2.5-years period. Results For the study of serum vs. plasma, 80 proteins were evaluable. The mean serum to EDTA plasma ratio ranged from 0.41–3.01. For 36 proteins, the serum and plasma values were not comparable due to high variability of the ratio, poor correlation, or possible concentration effect. For the bridging samples, the mean intra-study inter-assay coefficient of variation (CV) ranged from 11.3% to 26.1%. The mean inter-study CV was 42.0% before normalization and 26.2% after normalization. Inter-study results were well correlated (r ≥ 0.93), especially for studies using the same version of the panel (r ≥ 0.99). Conclusion For 44 of 92 proteins included in the Olink® I-O panel, the variation between results obtained using serum and EDTA plasma was constant and results were well correlated. Furthermore, samples could be stored for several years and used on different versions of the same PEA panel without it effecting results.

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Profiling of donor-specific immune effector signatures in response to rituximab in a human whole blood loop assay using blood from CLL patients

Cited by 6 publications

References 47 publications

Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy

Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy

An Adaptable Antibody‐Based Platform for Flexible Synthetic Peptide Delivery Built on Agonistic CD40 Antibodies

Determination of temporal reproducibility and variability of cancer biomarkers in serum and EDTA plasma samples using a proximity extension assay

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