Immunology and Immunogenetics

Immunology and Immunogenetics

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Dr. Clynes has more than 25 years of medical research experience with expertise in immuno-oncology discovery and development with several patents and more than 80 publications including in prestigious journals such as Science, Nature Medicine, Journal of Clinical Investigation and the Journal of Experimental Medicine.  Dr. Clynes has contributed to significant translational advances in medicine, including studies providing the rationale for engineering Fc domains to enhance the efficacy of antibody therapeutics in cancer, as well as proof-of-concept studies establishing the clinical utility of JAK and Syk protein tyrosine kinase inhibitors in T-cell-mediated autoimmunity. Prior to joining Xencor, Dr. Clynes served as group medical and scientific director of immuno-oncology in early clinical development at Bristol Myers Squibb. He was a co-founder of Vixen Pharmaceuticals (acquired by Aclaris Pharmaceuticals). Prior to joining BMS, he served as associate professor at Columbia University in the departments of medicine, microbiology, pathology and dermatology, where he was an NIH investigator with more than 20 years of continuous funding in cancer and autoimmunity. At Columbia, Dr. Clynes held several leadership positions, including head of the Laboratory of Cellular Immunology and Immunogenetics, head of the Flow Cytometry Translational Research Core, head of the Clinical Flow Cytometry/HLA laboratory and co-director of Tumor Immunology in the Irving Cancer Center. Dr. Clynes earned his medical degree and doctorate in biochemistry from Stony Brook University, and earned his bachelor's degree at the Massachusetts Institute of Technology. He also was a resident in internal medicine at the Barnes Hospital, St. Louis and a fellow in hematology and oncology at the Memorial Sloan-Kettering Cancer Center and Rockefeller University in New York. Dr. Clynes has participated as a consultant and scientific advisory board member with several biopharma companies and on numerous NIH and Research Foundation Scientific Review Committees. Dr. Clynes is the recipient of numerous honors including the Kimmel Scholar, Lupus Scholar, Arthritis Investigator and Cancer Research Institute Awards. Xencor is a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of autoimmune diseases, asthma and allergic diseases and cancer. Currently, 11 candidates engineered with Xencor's XmAb® technology are in clinical development internally and with partners. Xencor's internal programs include: XmAb®5871 in Phase 2 development for the treatment of IgG4-Related Disease, and also for the treatment of Systemic Lupus Erythematosus; XmAb®7195 in Phase 1 development for the treatment of asthma and allergic diseases; XmAb®14045 in Phase 1 development for acute myeloid leukemia; XmAb®13676 in Phase 1 development for B-cell malignancies; XmAb®18087 in pre-clinical development for the treatment of neuroendocrine tumors; and XmAb®20717 in pre-clinical development for the treatment of multiple cancers. Xencor's XmAb antibody engineering technology enables small changes to the structure of monoclonal antibodies resulting in new mechanisms of therapeutic action.  Xencor partners include Novartis, Amgen, MorphoSys, Merck, CSL/Janssen, Alexion and Boehringer Ingelheim. For more information, please visit www.xencor.com. Statements contained in this press release regarding matters that are not historical facts are forward-looking statements within the meaning of applicable securities laws, including any expectations relating to Xencor's staff composition, future growth trajectory, and intellectual property related to XmAb® Technology. Such statements involve known and unknown risks, uncertainties and other factors that may cause actual results, performance or achievements and the timing of events to be materially different from those implied by such statements, and therefore these statements should not be read as guarantees of future performance or results. Such risks include, without limitation, the risks associated with the process of discovering, developing, manufacturing and commercializing drugs that are safe and effective for use as human therapeutics and other risks described in Xencor's public securities filings. All forward-looking statements are based on Xencor's current information and belief as well as assumptions made by Xencor. Readers are cautioned not to place undue reliance on such statements and Xencor disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/xencor-appoints-raphael-clynes-md-phd-as-vice-president-of-translational-biology-300470263.html


Davidson F.,Clinical Biochemistry | Lock R.J.,Immunology and Immunogenetics
Annals of Clinical Biochemistry | Year: 2017

Background: Faecal calprotectin has been shown to be a useful non-invasive marker for the diagnosis and monitoring of inflammatory bowel disease in children and adults. Although there are well-established reference ranges for the diagnosis of inflammatory bowel disease in adults, these have been less well studied in children. The objective was to establish reference ranges in our local population. Method: All faecal calprotectin results from 2011 to 2014 were retrospectively collated and grouped according to patient age. Probability plots were used to determine expected upper limit of normal for each age group, and Mann-Whitney test was used to determine statistical difference between groups. Results: Upper limit of normal for age groups 1–3.9 years, 4–17.9 years and 18 years plus were 77, 62 and 61 µg/g, respectively. There was a significant difference (P = 0.0013) between the median calprotectin concentration for the age group 1–3.9 years (n = 87) and 4–17.9 years (n = 636) and between the age group 1–3.9 years and 18 years plus (n = 7953, P = 0.0001), but there was no significant difference between the age groups 4–17.9 years and 18 years plus (P = 0.4206). Conclusions: In our local population, faecal calprotectin varies with age. Children aged 1–3.9 years had higher concentrations of faecal calprotectin than adults, but there was no significant difference in faecal calprotectin between older children and adults. This is in agreement with other published studies; however, the faecal calprotectin upper limit of normal calculated for children aged 1–3.9 years was lower than has been observed elsewhere. © 2016, © The Author(s) 2016.


Egner W.,Sheffield Teaching Hospitals NHS TrustUK NEQAS ImmunologySheffield | Lock R.J.,Immunology and Immunogenetics | Patel D.,Sheffield Teaching Hospitals NHS TrustUK NEQAS ImmunologySheffield
Clinical and Experimental Immunology | Year: 2016

Immunoglobulin (Ig)G4 disease can have apparently 'normal' levels of IgG4 due to antigen excess conditions. IgG4 measurement therefore appears falsely low. UK National External Quality Assurance Scheme (UK NEQAS) data and other reports have suggested that this problem occurred despite pre-existing antigen excess detection steps. To determine the clinical relevance of the problem, we examined the prevalence and characteristics of prozoning in our laboratory and patient cohorts. We establish that the prevalence of raised IgG4 in routine IgG4 analysis is low (< 1%) using one of the two routine methods in use in the United Kingdom. We show that subsequent assay modification appears to have reduced the likelihood of misleading readings. However, the original version of the assay prozoned to low levels (below 0·64 g/l) in 41% of high IgG4 samples in our patients. This may explain the previous reports of low sensitivity of raised IgG4 for IgG4RD, and predictive values should be re-evaluated in this disease using modified prozone-resistant protocols. All laboratories providing IgG4 measurements should verify that their assays are fit for the clinical quality requirement of detection raised IgG4 levels and must verify the upper limit of their reference ranges and freedom from prozoning. © 2016 British Society for Immunology.


Egner W.,Sheffield Teaching Hospitals NHS Trust | Lock R.J.,Immunology and Immunogenetics | Patel D.,Sheffield Teaching Hospitals NHS Trust
Clinical and Experimental Immunology | Year: 2016

Immunoglobulin (Ig)G4 disease can have apparently ‘normal’ levels of IgG4 due to antigen excess conditions. IgG4 measurement therefore appears falsely low. UK National External Quality Assurance Scheme (UK NEQAS) data and other reports have suggested that this problem occurred despite pre-existing antigen excess detection steps. To determine the clinical relevance of the problem, we examined the prevalence and characteristics of prozoning in our laboratory and patient cohorts. We establish that the prevalence of raised IgG4 in routine IgG4 analysis is low (< 1%) using one of the two routine methods in use in the United Kingdom. We show that subsequent assay modification appears to have reduced the likelihood of misleading readings. However, the original version of the assay prozoned to low levels (below 0·64 g/l) in 41% of high IgG4 samples in our patients. This may explain the previous reports of low sensitivity of raised IgG4 for IgG4RD, and predictive values should be re-evaluated in this disease using modified prozone-resistant protocols. All laboratories providing IgG4 measurements should verify that their assays are fit for the clinical quality requirement of detection raised IgG4 levels and must verify the upper limit of their reference ranges and freedom from prozoning. © 2016 British Society for Immunology


PubMed | Sheffield., Sheffield Teaching Hospitals NHS Trust and Immunology and Immunogenetics
Type: Journal Article | Journal: Clinical and experimental immunology | Year: 2016

Immunoglobulin (Ig)G4 disease can have apparently normal levels of IgG4 due to antigen excess conditions. IgG4 measurement therefore appears falsely low. UK National External Quality Assurance Scheme (UK NEQAS) data and other reports have suggested that this problem occurred despite pre-existing antigen excess detection steps. To determine the clinical relevance of the problem, we examined the prevalence and characteristics of prozoning in our laboratory and patient cohorts. We establish that the prevalence of raised IgG4 in routine IgG4 analysis is low (< 1%) using one of the two routine methods in use in the United Kingdom. We show that subsequent assay modification appears to have reduced the likelihood of misleading readings. However, the original version of the assay prozoned to low levels (below 064 g/l) in 41% of high IgG4 samples in our patients. This may explain the previous reports of low sensitivity of raised IgG4 for IgG4RD, and predictive values should be re-evaluated in this disease using modified prozone-resistant protocols. All laboratories providing IgG4 measurements should verify that their assays are fit for the clinical quality requirement of detection raised IgG4 levels and must verify the upper limit of their reference ranges and freedom from prozoning.


Beck S.C.,Peterborough And Stamfords Nhs Foundation Trust | Lock R.J.,Immunology and Immunogenetics
Annals of Clinical Biochemistry | Year: 2015

‘Measurement uncertainty of measured quantity values’ (ISO15189) requires that the laboratory shall determine the measurement uncertainty for procedures used to report measured quantity values on patients’ samples. Where we have numeric data measurement uncertainty can be expressed as the standard deviation or as the co-efficient of variation. However, in immunology many of the assays are reported either as semi-quantitative (i.e. an antibody titre) or qualitative (positive or negative) results. In the latter context, measuring uncertainty is considerably more difficult. There are, however, strategies which can allow us to minimise uncertainty. A number of parameters can contribute to making measurements uncertain. These include bias, precision, standard uncertainty (expressed as standard deviation or coefficient of variation), sensitivity, specificity, repeatability, reproducibility and verification. Closely linked to these are traceability and standardisation. In this article we explore the challenges presented to immunology with regard to measurement uncertainty. Many of these challenges apply equally to other disciplines working with qualitative or semi-quantitative data. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.


PubMed | Peterborough and Stamfords NHS Foundation Trust and Immunology and Immunogenetics
Type: Journal Article | Journal: Annals of clinical biochemistry | Year: 2014

Measurement uncertainty of measured quantity values (ISO15189) requires that the laboratory shall determine the measurement uncertainty for procedures used to report measured quantity values on patients samples. Where we have numeric data measurement uncertainty can be expressed as the standard deviation or as the co-efficient of variation. However, in immunology many of the assays are reported either as semi-quantitative (i.e. an antibody titre) or qualitative (positive or negative) results. In the latter context, measuring uncertainty is considerably more difficult. There are, however, strategies which can allow us to minimise uncertainty. A number of parameters can contribute to making measurements uncertain. These include bias, precision, standard uncertainty (expressed as standard deviation or coefficient of variation), sensitivity, specificity, repeatability, reproducibility and verification. Closely linked to these are traceability and standardisation. In this article we explore the challenges presented to immunology with regard to measurement uncertainty. Many of these challenges apply equally to other disciplines working with qualitative or semi-quantitative data.


PubMed | Clinical Biochemistry and Immunology and Immunogenetics
Type: | Journal: Annals of clinical biochemistry | Year: 2016

Faecal calprotectin has been shown to be a useful non-invasive marker for the diagnosis and monitoring of inflammatory bowel disease in children and adults. Although there are well-established reference ranges for the diagnosis of inflammatory bowel disease in adults, these have been less well studied in children. The objective was to establish reference ranges in our local population.All faecal calprotectin results from 2011 to 2014 were retrospectively collated and grouped according to patient age. Probability plots were used to determine expected upper limit of normal for each age group, and Mann-Whitney test was used to determine statistical difference between groups.Upper limit of normal for age groups 1-3.9 years, 4-17.9 years and 18 years plus were 77, 62 and 61g/g, respectively. There was a significant difference (P=0.0013) between the median calprotectin concentration for the age group 1-3.9 years (n=87) and 4-17.9 years (n=636) and between the age group 1-3.9 years and 18 years plus (n=7953, P=0.0001), but there was no significant difference between the age groups 4-17.9 years and 18 years plus (P=0.4206).In our local population, faecal calprotectin varies with age. Children aged 1-3.9 years had higher concentrations of faecal calprotectin than adults, but there was no significant difference in faecal calprotectin between older children and adults. This is in agreement with other published studies; however, the faecal calprotectin upper limit of normal calculated for children aged 1-3.9 years was lower than has been observed elsewhere.

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