Imperacer (Immuno-PCR) method for ultra sensitive quantification of Interleukin-6 to support clinical phase III trial
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1
Chimera Biotec, Project Management, Germany
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2
Chimera Biotec, Assay Development, Germany
Purpose: Phamacodynamic (PD) markers such as cytokine Interleukin-6 (IL-6) have great impact on biotherapeutics development. Patient levels can vary between sub-pg/ml up to ng/ml concentrations, thereby surpassing narrow detection windows of standard ligand-binding assay (LBA) technologies. Additionally, available sample volume (e.g. from small animals or
multi-analyte studies) can be limited to <5-10μl.
Methods: We describe IL-6 Imperacer bioanalytical method development and validation in support of clinical phase III trials for autoimmune disorder therapies. Imperacer applies antibody-DNA detection conjugates and subsequent DNA amplification for high sensitivity and broad quantitative dynamic range. The assay was adapted to study requirements and validated for human serum and plasma samples from healthy and diseased individuals, respectively. An additional microsampling research protocol was evaluated, requiring only 1 μl sample for intra-assay double determination.
Results: IL-6 Imperacer complies to relevant guidelines for biomarker assays with lower limit of quantification (LLOQ) at 0.31
pg/ml, >4 orders of magnitude dynamic quantification range (up to 5 ng/ml), selectivity in spiked and non-spiked individuals,
and confirmed parallelism in serial 2fold and 3fold dilution of endogenous target. Up to 10 replicates for analysis were generated
from 100 μl sample volume in robust study sample analysis (>13,000 samples). Microsampling evaluation also revealed specific
separation of healthy/diseased individuals.
Conclusions: IL-6 Imperacer enabled flexible PD biomarker assessment in pre-clinical research setting (microsampling)
and clinical study support (validated high-throughput routine analysis). Imperacer technology is thereby a versatile tool for
biotherapeutics development.
Methods:
We describe IL-6 Imperacer bioanalytical method development and validation in support of clinical phase III trials for autoimmune disorder therapies. Imperacer applies antibody-DNA detection conjugates and subsequent DNA amplification for high sensitivity and broad quantitative dynamic range. The assay was adapted to study requirements and validated for human serum and plasma samples from healthy and diseased individuals, respectively. An additional microsampling research protocol was evaluated, requiring only 1 µl sample for intra-assay double determination
Results:
IL-6 Imperacer complies to relevant guidelines for biomarker assays with lower limit of quantification (LLOQ) at 0.31 pg/ml, >4 orders of magnitude dynamic quantification range (up to 5 ng/ml), selectivity in spiked and non-spiked individuals, and confirmed parallelism in serial 2fold and 3fold dilution of endogenous target. Up to 10 replicates for analysis were generated from 100 µl sample volume in robust study sample analysis (>13,000 samples). Microsampling evaluation also revealed specific separation of healthy/diseased individuals.
Conclusions:
IL-6 Imperacer enabled flexible PD biomarker assessment in pre-clinical research setting (microsampling) and clinical study support (validated high-throughput routine analysis).
Imperacer technology is thereby a versatile tool for biotherapeutics development.
Keywords:
biomarker,
Clinical support,
immuno-PCR,
IPCR,
ultra sensitive immunoassays
Conference:
EUFEMED 2017, London, United Kingdom, 17 May - 19 May, 2017.
Presentation Type:
Poster
Topic:
EUFEMED 2017 CONFERENCE
Citation:
Spengler
M,
Adler
M and
Pieper
C
(2019). Imperacer (Immuno-PCR) method for ultra sensitive quantification of Interleukin-6 to support clinical phase III trial.
Front. Pharmacol.
Conference Abstract:
EUFEMED 2017.
doi: 10.3389/conf.fphar.2017.62.00016
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Received:
29 Aug 2017;
Published Online:
25 Jan 2019.
*
Correspondence:
Dr. Mark Spengler, Chimera Biotec, Project Management, Bremen, Germany, spengler@chimera-biotec.com