'Fit-for-purpose' validation of SearchLight multiplex ELISAs of angiogenesis for clinical trial use.

2.50
Hdl Handle:
http://hdl.handle.net/10541/52813
Title:
'Fit-for-purpose' validation of SearchLight multiplex ELISAs of angiogenesis for clinical trial use.
Authors:
Backen, Alison C; Cummings, Jeffrey; Mitchell, Claire L; Jayson, Gordon C ( 0000-0002-8515-8944 ) ; Ward, Timothy H; Dive, Caroline ( 0000-0002-1726-8850 )
Abstract:
Validated assays of circulating biomarkers of angiogenesis to predict and determine the efficacy of vascular-targeted anticancer drugs would facilitate successful drug development. Multiple biomarker candidates exist and a multiplex approach was sought to minimise the requisite patient blood volume and to aid selection of those biomarkers with greatest potential clinical utility. Validation of the SearchLight multiplex ELISA platform comprising two multiplex assays of nine potential angiogenesis biomarkers was conducted (plex 1; VEGF R1 and R2, IL-8, KGF, PlGF; plex 2; PDGFbb, HGF, FGFb and VEGF). The study focused on instrument qualification, analyte specificity within the multiplex format, assay precision and reproducibility. No evidence was found within the multiplex that signals output from one analyte impinged on another or that antibody cross-reactivity occurred. Spike recovery for 5 between-experiment repeats was within +/-15% of input values for 7 of the 9 multiplexed analytes, with a coefficient of variation (CV) of <20% for 6 of the 9 analytes. Plasma samples from 8 ovarian cancer patients (who were not receiving therapy) were assessed using the two multiplexes on this platform to explore the likely baseline variability in this disease context. This study suggests that the platform and the multiplex approach will be useful to evaluate pharmacodynamic responses to vascular targeted therapy in early clinical trials.
Affiliation:
CR-UK Translational Angiogenesis Group, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester, M20 4BX, UK.
Citation:
'Fit-for-purpose' validation of SearchLight multiplex ELISAs of angiogenesis for clinical trial use. 2009, 342 (1-2):106-14 J. Immunol. Methods
Journal:
Journal of Immunological Methods
Issue Date:
15-Mar-2009
URI:
http://hdl.handle.net/10541/52813
DOI:
10.1016/j.jim.2009.01.003
PubMed ID:
19174166
Type:
Article
Language:
en
ISSN:
0022-1759
Appears in Collections:
All Paterson Institute for Cancer Research; Clinical and Experimental Pharmacology Group; Medical Oncology

Full metadata record

DC FieldValue Language
dc.contributor.authorBacken, Alison C-
dc.contributor.authorCummings, Jeffrey-
dc.contributor.authorMitchell, Claire L-
dc.contributor.authorJayson, Gordon C-
dc.contributor.authorWard, Timothy H-
dc.contributor.authorDive, Caroline-
dc.date.accessioned2009-03-07T17:05:14Z-
dc.date.available2009-03-07T17:05:14Z-
dc.date.issued2009-03-15-
dc.identifier.citation'Fit-for-purpose' validation of SearchLight multiplex ELISAs of angiogenesis for clinical trial use. 2009, 342 (1-2):106-14 J. Immunol. Methodsen
dc.identifier.issn0022-1759-
dc.identifier.pmid19174166-
dc.identifier.doi10.1016/j.jim.2009.01.003-
dc.identifier.urihttp://hdl.handle.net/10541/52813-
dc.description.abstractValidated assays of circulating biomarkers of angiogenesis to predict and determine the efficacy of vascular-targeted anticancer drugs would facilitate successful drug development. Multiple biomarker candidates exist and a multiplex approach was sought to minimise the requisite patient blood volume and to aid selection of those biomarkers with greatest potential clinical utility. Validation of the SearchLight multiplex ELISA platform comprising two multiplex assays of nine potential angiogenesis biomarkers was conducted (plex 1; VEGF R1 and R2, IL-8, KGF, PlGF; plex 2; PDGFbb, HGF, FGFb and VEGF). The study focused on instrument qualification, analyte specificity within the multiplex format, assay precision and reproducibility. No evidence was found within the multiplex that signals output from one analyte impinged on another or that antibody cross-reactivity occurred. Spike recovery for 5 between-experiment repeats was within +/-15% of input values for 7 of the 9 multiplexed analytes, with a coefficient of variation (CV) of <20% for 6 of the 9 analytes. Plasma samples from 8 ovarian cancer patients (who were not receiving therapy) were assessed using the two multiplexes on this platform to explore the likely baseline variability in this disease context. This study suggests that the platform and the multiplex approach will be useful to evaluate pharmacodynamic responses to vascular targeted therapy in early clinical trials.en
dc.language.isoenen
dc.subjectAngiogenesisen
dc.subjectBiomarkersen
dc.title'Fit-for-purpose' validation of SearchLight multiplex ELISAs of angiogenesis for clinical trial use.en
dc.typeArticleen
dc.contributor.departmentCR-UK Translational Angiogenesis Group, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester, M20 4BX, UK.en
dc.identifier.journalJournal of Immunological Methodsen

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