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Article ; Online: GIPR gene expression in testis is mouse specific and can impact male mouse fertility.

Killion, Elizabeth A / Hussien, Rajaa / Shkumatov, Artem / Davies, Rhian / Lloyd, David J / Véniant, Murielle M / Lebrec, Herve / Fort, Madeline M

Andrology

2022 Volume 10, Issue 4, Page(s) 789–799

Abstract: Background: Glucose-dependent insulinotropic polypeptide receptor (Gipr) gene expression has been reported in mouse spermatids and Gipr knockout male mice have previously been reported to have decreased in vitro fertilization, although the role of Gipr ... ...

Abstract	Background: Glucose-dependent insulinotropic polypeptide receptor (Gipr) gene expression has been reported in mouse spermatids and Gipr knockout male mice have previously been reported to have decreased in vitro fertilization, although the role of Gipr signaling in male mouse fertility is not well understood. Objectives: The purposes of these studies were to determine the role of glucose-dependent insulinotropic polypeptide receptor in male fertility using Gipr knockout mice and anti-glucose-dependent insulinotropic polypeptide receptor antibody-treated wild-type mice and to determine if the expression of Gipr in mouse testes is similar in non-human and human primates. Methods and materials: Adiponectin promoter-driven Gipr knockout male mice (Gipr Results: Gipr Discussion: The infertility of Gipr Conclusion: Our data support a role for Gipr expression in the mouse testis during the development of sperm fertilization potential, but based on gene expression data, a similar role for glucose-dependent insulinotropic polypeptide receptor in non-human primate or human male fertility is unlikely.
MeSH term(s)	Animals ; Female ; Fertility ; Gastric Inhibitory Polypeptide/genetics ; Gastric Inhibitory Polypeptide/metabolism ; Gene Expression ; Humans ; Macaca fascicularis/genetics ; Macaca fascicularis/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; RNA, Messenger/metabolism ; Receptors, G-Protein-Coupled/genetics ; Receptors, Gastrointestinal Hormone ; Sperm Motility ; Testis/metabolism
Chemical Substances	RNA, Messenger ; Receptors, G-Protein-Coupled ; Receptors, Gastrointestinal Hormone ; Gastric Inhibitory Polypeptide (59392-49-3) ; gastric inhibitory polypeptide receptor (D6H00MV7K8)
Language	English
Publishing date	2022-03-08
Publishing country	England
Document type	Journal Article
ZDB-ID	2696108-8
ISSN	2047-2927 ; 2047-2919
ISSN (online)	2047-2927
ISSN	2047-2919
DOI	10.1111/andr.13166
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Zs.A 6983: Show issues

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Article ; Online: Glucose-Dependent Insulinotropic Polypeptide Receptor Therapies for the Treatment of Obesity, Do Agonists = Antagonists?

Killion, Elizabeth A / Lu, Shu-Chen / Fort, Madeline / Yamada, Yuichiro / Véniant, Murielle M / Lloyd, David J

Endocrine reviews

2019 Volume 41, Issue 1

Abstract: Glucose-dependent insulinotropic polypeptide receptor (GIPR) is associated with obesity in human genome-wide association studies. Similarly, mouse genetic studies indicate that loss of function alleles and glucose-dependent insulinotropic polypeptide ... ...

Abstract	Glucose-dependent insulinotropic polypeptide receptor (GIPR) is associated with obesity in human genome-wide association studies. Similarly, mouse genetic studies indicate that loss of function alleles and glucose-dependent insulinotropic polypeptide overexpression both protect from high-fat diet-induced weight gain. Together, these data provide compelling evidence to develop therapies targeting GIPR for the treatment of obesity. Further, both antagonists and agonists alone prevent weight gain, but result in remarkable weight loss when codosed or molecularly combined with glucagon-like peptide-1 analogs preclinically. Here, we review the current literature on GIPR, including biology, human and mouse genetics, and pharmacology of both agonists and antagonists, discussing the similarities and differences between the 2 approaches. Despite opposite approaches being investigated preclinically and clinically, there may be viability of both agonists and antagonists for the treatment of obesity, and we expect this area to continue to evolve with new clinical data and molecular and pharmacological analyses of GIPR function.
MeSH term(s)	Animals ; Anti-Obesity Agents/therapeutic use ; Genome-Wide Association Study ; Humans ; Mice ; Molecular Targeted Therapy/methods ; Molecular Targeted Therapy/trends ; Obesity/drug therapy ; Obesity/genetics ; Receptors, Gastrointestinal Hormone/antagonists & inhibitors ; Receptors, Gastrointestinal Hormone/genetics ; Receptors, Gastrointestinal Hormone/physiology
Chemical Substances	Anti-Obesity Agents ; Receptors, Gastrointestinal Hormone ; gastric inhibitory polypeptide receptor (D6H00MV7K8)
Language	English
Publishing date	2019-09-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	603096-8
ISSN	1945-7189 ; 0163-769X
ISSN (online)	1945-7189
ISSN	0163-769X
DOI	10.1210/endrev/bnz002
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Zs.A 1562: Show issues

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Article ; Online: Demographics and deprivation in obstetric brachial plexus palsy: a retrospective cohort study.

Hardie, Claire Madeline / Bourke, Grainne / Salt, Emily / Fort-Schaale, Alice / Clark, Stephen / Wiberg, Mikael / Bains, Robert

The Journal of hand surgery, European volume

2023 , Page(s) 17531934231196421

Abstract: The present study analyses the relationships between deprivation and obstetric brachial plexus palsy (OBPP). A retrospective observational study was conducted of infants with OBPP seen between 2008 and 2020 ( ...

Abstract	The present study analyses the relationships between deprivation and obstetric brachial plexus palsy (OBPP). A retrospective observational study was conducted of infants with OBPP seen between 2008 and 2020 (
Language	English
Publishing date	2023-09-11
Publishing country	England
Document type	Journal Article
ZDB-ID	2272801-6
ISSN	2043-6289 ; 1753-1934
ISSN (online)	2043-6289
ISSN	1753-1934
DOI	10.1177/17531934231196421
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Zs.A 1940: Show issues

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Article ; Online: Assessment of the performance of three multiplex array panels for the detection of circulating cytokines and chemokines in naive, LPS, and SEB-treated cynomolgus macaques.

He, Ching / Narayanan, Padma K / Fort, Madeline M

Toxicologic pathology

2014 Volume 42, Issue 1, Page(s) 286–292

Abstract: To assess relative sensitivity for detection of cytokines and chemokines in cynomolgus serum samples, we tested three commercially available multiplex array kits using the Luminex® platform with sera from animals exposed by intravenous injection to 150 ... ...

Abstract	To assess relative sensitivity for detection of cytokines and chemokines in cynomolgus serum samples, we tested three commercially available multiplex array kits using the Luminex® platform with sera from animals exposed by intravenous injection to 150 μg/kg staphylococcal enterotoxin B (SEB) or 20 μg/kg lipopolysaccharide (LPS). Each of these kits detected similar patterns of changes in circulating cytokines/chemokines in response to SEB or LPS stimulation, especially the induction of high amounts of interleukin (IL)-2 and interferon-gamma (IFN-γ) in response to SEB but not LPS. However, there were clear differences in sensitivity for particular analytes, especially for IL-10. Additional experiments that focused on one multiplex array kit demonstrated very low or undetectable levels of cytokines in naive cynomolgus macaques, except for highly variable background levels of IL-8, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1β. Therefore, multiplex array analysis of circulating cytokine/chemokine patterns was capable of detection of systemic activation of diverse immune cell subsets.
MeSH term(s)	Administration, Intravenous ; Animals ; Chemokine CCL2/blood ; Chemokine CCL4/blood ; Enterotoxins/administration & dosage ; Enterotoxins/adverse effects ; Female ; Interferon-gamma/blood ; Interleukin-10/blood ; Interleukin-2/blood ; Interleukin-8/blood ; Lipopolysaccharides/administration & dosage ; Lipopolysaccharides/adverse effects ; Macaca fascicularis/immunology ; Male ; Protein Array Analysis/methods ; Reagent Kits, Diagnostic
Chemical Substances	Chemokine CCL2 ; Chemokine CCL4 ; Enterotoxins ; Interleukin-2 ; Interleukin-8 ; Lipopolysaccharides ; Reagent Kits, Diagnostic ; Interleukin-10 (130068-27-8) ; enterotoxin B, staphylococcal (39424-53-8) ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2014-01
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	841009-4
ISSN	1533-1601 ; 0192-6233
ISSN (online)	1533-1601
ISSN	0192-6233
DOI	10.1177/0192623313510363
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Zs.A 1975: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 473: Show issues

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Article ; Online: Current Concepts in Natural Killer Cell Biology and Application to Drug Safety Assessments.

Goyos, Ana / Fort, Madeline / Sharma, Amy / Lebrec, Herve

Toxicological sciences : an official journal of the Society of Toxicology

2019 Volume 170, Issue 1, Page(s) 10–19

Abstract: Natural killer (NK) cells are lymphocytes capable of cytotoxicity against virally infected cells and tumor cells. The display of effector function by NK cells is the result of interactions between germline encoded activating/inhibitory NK cell receptors ... ...

Abstract	Natural killer (NK) cells are lymphocytes capable of cytotoxicity against virally infected cells and tumor cells. The display of effector function by NK cells is the result of interactions between germline encoded activating/inhibitory NK cell receptors and their ligands (major histocompatibility complex class I, major histocompatibility complex class I-like, viral, and cellular stress-related surface molecules) expressed on target cells. Determination of NK cell number and function is a common element of the immunotoxicology assessment paradigm for the development of certain classes of pharmaceuticals across a range of modalities. This article summarizes the evidence associating NK cell dysfunction with infectious and cancer risks, reviews emerging NK cell biology, including the impact of immunogenetics on NK cell education and function, and provides perspectives about points to consider when assessing NK cell function in different species in the context of safety assessment.
MeSH term(s)	Animals ; Cytotoxicity, Immunologic ; Disease Resistance/drug effects ; Disease Resistance/immunology ; Dose-Response Relationship, Drug ; Drug-Related Side Effects and Adverse Reactions/immunology ; HLA Antigens/metabolism ; Histocompatibility Antigens Class I/metabolism ; Humans ; Killer Cells, Natural/drug effects ; Killer Cells, Natural/immunology ; Killer Cells, Natural/metabolism ; Ligands ; Pharmaceutical Preparations/administration & dosage ; Receptors, Natural Killer Cell/metabolism
Chemical Substances	HLA Antigens ; Histocompatibility Antigens Class I ; Ligands ; Pharmaceutical Preparations ; Receptors, Natural Killer Cell
Language	English
Publishing date	2019-04-24
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1420885-4
ISSN	1096-0929 ; 1096-6080
ISSN (online)	1096-0929
ISSN	1096-6080
DOI	10.1093/toxsci/kfz098
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Zs.A 1709: Show issues

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Article ; Online: Manipulation of regulatory T-cell function by immunomodulators: a boon or a curse?

Fort, Madeline M / Narayanan, Padma K

Toxicological sciences : an official journal of the Society of Toxicology

2010 Volume 117, Issue 2, Page(s) 253–262

Abstract: Regulatory T cells (Tregs) constitute a subset of lymphocytes that have the capability of suppressing immune responses in vivo and in vitro both directly by cell-cell contact and indirectly through the production of anti-inflammatory cytokines, such as ... ...

Abstract	Regulatory T cells (Tregs) constitute a subset of lymphocytes that have the capability of suppressing immune responses in vivo and in vitro both directly by cell-cell contact and indirectly through the production of anti-inflammatory cytokines, such as interleukin-10 and tumor growth factor-β. Tregs constitute a small subset of T lymphocytes, yet their presence can prevent and control autoimmune disease and organ transplant rejection and contribute to maternal tolerance of fetal alloantigens, whereas their absence results in uncontrolled inflammation. But Treg function may not always be considered beneficial: There is growing evidence that the immunosuppressive effects of Tregs are also associated with growth of tumor cells. Thus, Tregs are of considerable medical interest as targets for the treatment of both inflammatory diseases and cancer. In this review of published literature, we describe some well-characterized immunomodulatory drugs and environmental toxicants that can either positively or negatively affect the number and/or function of Tregs in animal models and/or human patients. The targeted suppression or enhancement of Treg function needs to be carefully considered in immunotoxicity evaluations as manipulation of this immune cell population could result in undesired consequences, including decreased host resistance, decreased fertility, or increased incidence of inflammatory disease.
MeSH term(s)	Animals ; Cell Count ; Disease Models, Animal ; Forkhead Transcription Factors/immunology ; Forkhead Transcription Factors/metabolism ; Humans ; Immune System/drug effects ; Immune System/immunology ; Immunologic Factors/toxicity ; Mice ; Species Specificity ; T-Lymphocytes, Regulatory/drug effects ; T-Lymphocytes, Regulatory/immunology
Chemical Substances	FOXP3 protein, human ; Forkhead Transcription Factors ; Foxp3 protein, mouse ; Immunologic Factors
Language	English
Publishing date	2010-10
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1420885-4
ISSN	1096-0929 ; 1096-6080
ISSN (online)	1096-0929
ISSN	1096-6080
DOI	10.1093/toxsci/kfq136
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Zs.A 1709: Show issues

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Article ; Online: Determination of absolute counts of circulating regulatory T cells in cynomolgus macaques using an optimized flow cytometric method.

Clark, Stacie M / Narayanan, Padma K / Fort, Madeline M

Toxicologic pathology

2012 Volume 40, Issue 1, Page(s) 107–112

Abstract: Regulatory T cells (Tregs) are a rare subset of lymphocytes that inhibit the activation and effector functions of T cells and are important regulators of immune responses. Although Tregs are well characterized in humans and rodents, little is known about ...

Abstract	Regulatory T cells (Tregs) are a rare subset of lymphocytes that inhibit the activation and effector functions of T cells and are important regulators of immune responses. Although Tregs are well characterized in humans and rodents, little is known about their immunophenotyping (IP) profile in cynomolgus macaques (Macaca fascicularis), which is an important species for pharmacological and toxicological evaluation of potential immune modulators because of their similar physiologic, genetic, and metabolic response patterns to humans. The authors have developed an immunophenotyping panel using a high-throughput 96-well microtiter plate-based assay to detect circulating Tregs (CD3(+)CD4(+)CD25(hi)FoxP3(+)) and have determined the normal range for the number of Tregs in naive healthy cynomolgus macaques to be 56.4 to 179.7 cells/µL (mean ± SEM = 113.6 ± 5.1 cells/µL; n = 25). Furthermore, the authors compared the resulting FoxP3(+) Treg profiles with a CD127(lo) cell-surface panel (CD3(+)CD4(+)CD25(hi) CD127(lo)) and found a close correlation between the absolute numbers of CD3(+)CD4(+)CD25(hi)FoxP3(+) and CD3(+)CD4(+)CD25(hi)CD127(lo) cells (mean ± SD = 120 ± 8.0 cells/µL). Quantification of circulating Tregs in cynomolgus macaques in this high-throughput assay may help to identify drug candidates that affect this rare, but critical, immunoregulatory cell population.
MeSH term(s)	Animals ; Antigens, CD/blood ; Female ; Flow Cytometry/methods ; Forkhead Transcription Factors/blood ; High-Throughput Screening Assays ; Immunophenotyping/methods ; Macaca fascicularis/blood ; Macaca fascicularis/immunology ; Male ; Models, Animal ; T-Lymphocytes, Regulatory/chemistry ; T-Lymphocytes, Regulatory/cytology
Chemical Substances	Antigens, CD ; Forkhead Transcription Factors
Language	English
Publishing date	2012
Publishing country	United States
Document type	Journal Article
ZDB-ID	841009-4
ISSN	1533-1601 ; 0192-6233
ISSN (online)	1533-1601
ISSN	0192-6233
DOI	10.1177/0192623311425056
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Zs.A 1975: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 473: Show issues

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Article ; Online: MRGPRX2 activation as a rapid, high-throughput mechanistic-based approach for detecting peptide-mediated human mast cell degranulation liabilities.

Lafleur, Marc A / Werner, Jonathan / Fort, Madeline / Lobenhofer, Edward K / Balazs, Mercedesz / Goyos, Ana

Journal of immunotoxicology

2020 Volume 17, Issue 1, Page(s) 110–121

Abstract: Mast cells play key roles in allergy, anaphylaxis/anaphylactoid reactions, and defense against pathogens/toxins. These cells contain cytoplasmic granules with a wide spectrum of pleotropic mediators that are released upon activation. While mast cell ... ...

Abstract	Mast cells play key roles in allergy, anaphylaxis/anaphylactoid reactions, and defense against pathogens/toxins. These cells contain cytoplasmic granules with a wide spectrum of pleotropic mediators that are released upon activation. While mast cell degranulation (MCD) occurs upon clustering of the IgE receptor bound to IgE and antigen, MCD is also triggered through non-IgE-mediated mechanisms, one of which is via Mas-related G protein-coupled receptor X2 (MRGPRX2). MRGPRX2 can be activated by many basic biogenic amines and peptides. Consequently, MRGPRX2-mediated MCD is an important potential safety liability for peptide therapeutics. To facilitate peptide screening for this liability in early preclinical drug development, a rapid, high-throughput engineered CHO-K1 cell-based MRGPRX2 activation assay was evaluated and compared to histamine release in CD34
MeSH term(s)	Antigens, CD34/metabolism ; Cell Degranulation/drug effects ; Cell Degranulation/immunology ; Cell Engineering ; Cells, Cultured ; Cytotoxicity Tests, Immunologic/methods ; Drug Evaluation, Preclinical/methods ; Hematopoietic Stem Cell Mobilization ; Hematopoietic Stem Cells/metabolism ; High-Throughput Screening Assays/methods ; Histamine/analysis ; Histamine/metabolism ; Humans ; Mast Cells/drug effects ; Mast Cells/immunology ; Mast Cells/metabolism ; Nerve Tissue Proteins/metabolism ; Peptides/adverse effects ; Primary Cell Culture ; Receptors, G-Protein-Coupled/metabolism ; Receptors, Neuropeptide/metabolism ; Sensitivity and Specificity
Chemical Substances	Antigens, CD34 ; MRGPRX2 protein, human ; Nerve Tissue Proteins ; Peptides ; Receptors, G-Protein-Coupled ; Receptors, Neuropeptide ; Histamine (820484N8I3)
Language	English
Publishing date	2020-06-10
Publishing country	England
Document type	Evaluation Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2205064-4
ISSN	1547-6901 ; 1547-691X
ISSN (online)	1547-6901
ISSN	1547-691X
DOI	10.1080/1547691X.2020.1757793
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Zs.A 6167: Show issues

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Article ; Online: Cytokine release: A workshop proceedings on the state-of-the-science, current challenges and future directions.

Grimaldi, Christine / Finco, Deborah / Fort, Madeline M / Gliddon, Daniel / Harper, Kirsty / Helms, Whitney S / Mitchell, Jane A / O'Lone, Raegan / Parish, Stanley T / Piche, Marie-Soleil / Reed, Daniel M / Reichmann, Gabriele / Ryan, Patricia C / Stebbings, Richard / Walker, Mindi

Cytokine

2016 Volume 85, Page(s) 101–108

Abstract: In October 2013, the International Life Sciences Institute - Health and Environmental Sciences Institute Immunotoxicology Technical Committee (ILSI-HESI ITC) held a one-day workshop entitled, "Workshop on Cytokine Release: State-of-the-Science, Current ... ...

Abstract	In October 2013, the International Life Sciences Institute - Health and Environmental Sciences Institute Immunotoxicology Technical Committee (ILSI-HESI ITC) held a one-day workshop entitled, "Workshop on Cytokine Release: State-of-the-Science, Current Challenges and Future Directions". The workshop brought together scientists from pharmaceutical, academic, health authority, and contract research organizations to discuss novel approaches and current challenges for the use of in vitro cytokine release assays (CRAs) for the identification of cytokine release syndrome (CRS) potential of novel monoclonal antibody (mAb) therapeutics. Topics presented encompassed a regulatory perspective on cytokine release and assessment, case studies regarding the translatability of preclinical cytokine data to the clinic, and the latest state of the science of CRAs, including comparisons between mAb therapeutics within one platform and across several assay platforms, a novel physiological assay platform, and assay optimization approaches such as determination of FcR expression profiles and use of statistical tests. The data and approaches presented confirmed that multiple CRA platforms are in use for identification of CRS potential and that the choice of a particular CRA platform is highly dependent on the availability of resources for individual laboratories (e.g. positive and negative controls, number of human blood donors), the assay through-put required, and the mechanism-of-action of the therapeutic candidate to be tested. Workshop participants agreed that more data on the predictive performance of CRA platforms is needed, and current efforts to compare in vitro assay results with clinical cytokine assessments were discussed. In summary, many laboratories continue to focus research efforts on the improvement of the translatability of current CRA platforms as well explore novel approaches which may lead to more accurate, and potentially patient-specific, CRS prediction in the future.
Language	English
Publishing date	2016
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1018055-2
ISSN	1096-0023 ; 1043-4666
ISSN (online)	1096-0023
ISSN	1043-4666
DOI	10.1016/j.cyto.2016.06.006
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Zs.A 2840: Show issues

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Article ; Online: Development of the first reference antibody panel for qualification and validation of cytokine release assay platforms - Report of an international collaborative study.

Vessillier, Sandrine / Fort, Madeline / O'Donnell, Lynn / Hinton, Heather / Nadwodny, Kimberly / Piccotti, Joseph / Rigsby, Peter / Staflin, Karin / Stebbings, Richard / Mekala, Divya / Willingham, Aarron / Wolf, Babette

Cytokine: X

2020 Volume 2, Issue 4, Page(s) 100042

Abstract: Immunomodulatory therapeutics such as monoclonal antibodies (mAb) carry an inherent risk of undesired immune reactions. One such risk is cytokine release syndrome (CRS), a rapid systemic inflammatory response characterized by the secretion of pro- ... ...

Abstract	Immunomodulatory therapeutics such as monoclonal antibodies (mAb) carry an inherent risk of undesired immune reactions. One such risk is cytokine release syndrome (CRS), a rapid systemic inflammatory response characterized by the secretion of pro-inflammatory cytokines from immune cells. It is crucial for patient safety to correctly identify potential risk of CRS prior to first-in-human dose administration. For this purpose, a variety of in vitro cytokine release assays (CRA) are routinely used as part of the preclinical safety assessment of novel therapeutic mAbs. One of the challenges for the development and comparison of CRA performance is the lack of availability of standard positive and negative control mAbs for use in assay qualification. To address this issue, the National Institute for Biological Standards and Control (NIBSC) developed a reference panel of lyophilised mAbs known to induce CRS in the clinic: human anti-CD52, mouse anti-CD3 and human superagonistic (SA) anti-CD28 mAb manufactured according to the respective published sequences of Campath-1H® (alemtuzumab, IgG1) , Orthoclone OKT-3® (muromonab, IgG2a) and TGN1412 (theralizumab, IgG4), as well as three isotype matched negative controls (human IgG1, mouse IgG2a and human IgG4, respectively). The relative capacity of these control mAbs to stimulate the release of IFN-γ, IL-2, TNF-α and IL-6 in vitro was evaluated in eleven laboratories in an international collaborative study mediated through the HESI Immuno-safety Technical Committee Cytokine Release Assay Working Group. Participants tested the NIBSC mAbs in a variety of CRA platforms established at each institution. This paper presents the results from the centralised cytokine quantification on all the plasma/supernatants corresponding to the stimulation of immune cells in the different CRA platforms by a single concentration of each mAb. Each positive control mAb induced significant cytokine release in most of the tested CRA platforms. There was a high inter-laboratory variability in the levels of cytokines produced, but similar patterns of response were observed across laboratories that replicated the cytokine release patterns previously published for the respective clinical therapeutic mAbs. Therefore, the positive and negative mAbs are suitable as a reference panel for the qualification and validation of CRAs, comparison of different CRA platforms (e.g. solid vs aqueous phase), and intra- and inter-laboratory comparison of CRA performance. Thus, the use of this panel of positive and negative control mAbs will increase the confidence in the robustness of a CRA platform to identify a potential CRS risk for novel immunomodulatory therapeutic candidates.
Language	English
Publishing date	2020-12-15
Publishing country	Netherlands
Document type	Journal Article
ISSN	2590-1532
ISSN (online)	2590-1532
DOI	10.1016/j.cytox.2020.100042
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