Cherry Edwards

National Institute for Biological Standards and Control

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Richard Stebbings

National Institute for Biological Standards and Control

David North

National Institute for Biological Standards and Control

Robin Thorpe

National Institute for Biological Standards and Control

Jan W. Gratama

Gelre Hospitals

David Ferguson

John Radcliffe Hospital

Stuart J. Brown

Cell Therapy Catapult

Lucy Findlay

National Institute for Biological Standards and Control

William Elsley

National Institute for Biological Standards and Control

Herman Waldmann

University of Oxford

Michael Papamichail

National Institute for Health Research

Cooperative Institutions

National Institute for Biological Standards and Control

University of Hertfordshire

University College London

Potters Bar Community Hospital

University of Oxford

John Wiley & Sons (United States)

Imperial College London

Scottish National Blood Transfusion Service

The Royal Free Hospital

Istituto Nazionale di Fisica Nucleare, Sezione di Milano

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

“Cytokine Storm” in the Phase I Trial of Monoclonal Antibody TGN1412: Better Understanding the Causes to Improve PreClinical Testing of Immunotherapeutics

The Journal of Immunology (2007)

Richard Stebbings Lucy Findlay Cherry Edwards David Eastwood Chris Bird

Abstract The CD28-specific mAb TGN1412 rapidly caused a life-threatening “cytokine storm” in all six healthy volunteers in the Phase I clinical trial of this superagonist, signaling a failure of preclinical safety testing. We report novel in vitro procedures in which TGN1412, immobilized in various ways, is presented to human white blood cells in a manner that stimulates the striking release of cytokines and profound lymphocyte proliferation that occurred in vivo in humans. The novel procedures would have predicted the toxicity of this superagonist and are now being applied to emerging immunotherapeutics and to other therapeutics that have the potential to act upon the immune system. Data from these novel procedures, along with data from in vitro and in vivo studies in nonhuman primates, suggest that the dose of TGN1412 given to human volunteers was close to the maximum immunostimulatory dose and that TGN1412 is not a superagonist in nonhuman primates.

Cytokine Storm

10.4049/jimmunol.179.5.3325

Cite

Citations (307)

Developing an Interactive Methodology: A Co-operative Approach. Occasional Papers, 27.

Cherry Edwards Michael Grenfell

Source

Cite

Citations (0)

Multicentre evaluation of stable reference whole blood for enumeration of lymphocyte subsets by flow cytometry

Cytometry Part B Clinical Cytometry (2005)

Cherry Edwards Danielle Belgrave George Janossy Nicholas J. Bradley Richard Stebbings

BACKGROUND: Clinical indications for lymphocyte subset enumeration by flow cytometry include monitoring of disease progression and timing of therapeutic intervention in infection with human immunodeficiency virus. Until recently international standardisation has not been possible due to a lack of suitable stable reference material. METHODS: This study consisted of two trials of a stabilised whole blood preparation. Eleven participants were sent two standard protocols for staining plus gating strategy and asked to report absolute counts for lymphocyte subsets. RESULTS: No significant difference was detected between the two methods when results from the two assays and all partners were pooled. Significant differences in results from the different partners were observed. However, representative mean counts were obtained for geometric means, geometric coefficient of variation, and 95% confidence interval for CD3 910 cells/mul, 9%, and 888 to 933, respectively), CD4 (495 cells/mul, 12%, and 483 to 507), and CD8 (408 cells/mul, 13%, and 393 to 422). CONCLUSION: We have introduced a stabilised blood preparation and a well-characterized biological standard. The availability of this reference material greatly simplifies the validation of new techniques for CD4(+) T-cell enumeration and the expansion of external quality assurance programmes for clinical laboratories, including those that operate in resource-restricted environments. (c) 2005 Wiley-Liss, Inc.

Enumeration

Cytometry

10.1002/cyto.b.20061

Cite

Citations (3)

CD8 ⁺ Lymphocytes Do Not Mediate Protection against Acute Superinfection 20 Days after Vaccination with a Live Attenuated Simian Immunodeficiency Virus

Journal of Virology (2005)

Richard Stebbings Neil Berry Herman Waldmann Pru Bird G Hale

In order to test the hypothesis that CD8+ cytotoxic T lymphocytes mediate protection against acute superinfection, we depleted >99% of CD8+ lymphocytes in live attenuated simian immunodeficiency virus macC8 (SIVmacC8) vaccinees from the onset of vaccination, maintained that depletion for 20 days, and then challenged with pathogenic, wild-type SIVmacJ5. Vaccinees received 5 mg per kg of humanized anti-CD8 monoclonal antibody (MAb) 1 h before inoculation, followed by the same dose again on days 3, 7, 10, 13, and 17. On day 13, peripheral CD8+ T lymphocytes were >99% depleted in three out of four anti-CD8 MAb-treated vaccinees. At this time attenuated SIVmacC8 viral RNA loads in anti-CD8 MAb-treated vaccinees were significantly higher than control vaccinees treated contemporaneously with nonspecific human immunoglobulin. Lymphoid tissue CD8+ T lymphocyte depletion was >99% in three out of four anti-CD8 MAb-treated vaccinees on the day of wild-type SIVmacJ5 challenge. All four control vaccinees and three out of four anti-CD8 MAb-treated vaccinees were protected against detectable superinfection with wild-type SIVmacJ5. Although superinfection with wild-type SIVmacJ5 was detected at postmortem in a single anti-CD8 MAb-treated vaccinee, this did not correlate with the degree of preceding CD8+ T lymphocyte depletion. Clearance of attenuated SIVmacC8 viremia coincided with recovery of normal CD8+ T lymphocyte counts between days 48 and 76. These results support the view that cytotoxic T lymphocytes are important for host-mediated control of SIV primary viremia but do not indicate a central role in protection against acute superinfection conferred by inoculation with live attenuated SIV.

Superinfection

Viremia

Simian immunodeficiency virus

10.1128/jvi.79.19.12264-12272.2005

Cite

Citations (35)

An evaluation of support groups for patients with long-term chronic pain and complex psychosocial difficulties

European Journal of Psychotherapy & Counselling (2005)

Andrew R. Arthur Cherry Edwards

There is a significant group of chronic pain patients with complex psychosocial needs who are frequent users of hospital outpatient departments and who do not participate in or benefit from traditional pain management treatments and are convinced there is a medical solution to their problems. They are a particularly challenging group of patients to help, often shunned by medical and psychological professionals. A new type of ten-session psycho-social group for these patients that is less demanding than traditional pain management group programmes is investigated. It is designed to foster the development into community-based self-help groups and reduce the need for professional support and unnecessary medical intervention. Accounts of four groups of patients who participated in support groups and successfully established their own groups is presented. To assess changes in motivation, mood and pain disability standardized questionnaire measures were given before and after group attendance. Findings suggest that patients benefited and took increased responsibility for their pain management but did not demonstrate positive changes on measures of mood or level of pain disability. Patients experienced satisfaction with the groups and established their own self-help community groups. The positive experience of participants and staff suggests further work with support groups would be productive for this group of patients.

Attendance

Support group

Outpatient clinic

10.1080/13642530500249761

Cite

Citations (9)