Innovative bioanalytical solutions to solve challenges of new therapeutics

The growth of precision medicines and technologies to assess disease states are improving, accelerating the practice of medicine and improving patient lives. Not only are newer therapeutic modalities requiring advances in bioanalytical assays, but advances in biomarker technologies are enabling improved measures of disease progression and therapy efficacy. An effective bioanalytical strategy must be robust and adapt to changing needs as the data generated within your program is converted to an in-depth understanding of your drug and its action in treating the disease.

Join us for a series of roundtable discussions to explore key considerations of flow cytometry for cellular biomarkers and advances in the utilization of aptamer capture reagents for LC–MS/MS analysis of proteins that are impacting bioanalytical strategies.

High-sensitivity flow cytometry and the detection of minimal residual disease

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Flow cytometry is a complex technology that allows multiparametric measurements on a high number of single cells. Thanks to this high-throughput, flow cytometry is a highly sensitive technique that can be utilized for the detection of very rare cell populations. It is then no surprise that in the clinical field, it has become the platform of choice in the detection of MRD in various types of leukemia. The determination of MRD in cancer patients is of great clinical interest as it can be utilized as a good indicator of cancer prognosis and the likelihood of relapse. Thus, MRD detection is increasingly being proposed as a potential surrogate endpoint for clinical trials.

In recent years, we have developed and validated highly sensitive flow cytometry assays for MRD detection in acute myeloid leukemia, chronic lymphoid leukemia and multiple myeloma for primary and/or secondary endpoint utilization in clinical trials. In this presentation, we will review the general utilization for flow cytometry in MRD detection and will take the audience through the results of a recent validation that was performed for MM MRD flow assay.

What will you learn?

  • High-sensitivity flow cytometry allowing for the detection of MRD and how it can be utilized in the context of clinical trials
  • How high analytical and functional sensitivity can be achieved utilizing flow cytometry
  • The logistical, operational and scientific challenges of validating such flow assays

Speaker

Christèle Gonneau

Lead Scientist, Flow Cytometry, Labcorp Drug Development (Geneva, Switzerland)

Christèle graduated with a BSc in molecular biology from Florida Institute of Technology (FL, USA) and an MSc in human reproductive biology from Imperial College London (London, UK). She then specialized in the field of stem cell biology and completed her PhD at the University of Edinburgh (Edinburgh, Scotland) and her postdoctoral training at the École Polytechnique Fédérale De Lausanne (Lausanne, Switzerland). Christèle joined Covance (now Labcorp Drug Development) Central Laboratory Services in July 2014 as a Staff Scientist in flow cytometry and became Lead Scientist in April 2018. She currently leads the development and validation of new flow cytometry assays to be utilized for global clinical trials.

Aptamers as affinity reagents for hybrid LBA/LC–MS: preclinical bioanalysis of human IgG therapeutics

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Bioanalysis of protein therapeutics by LC–MS is increasingly utilized as a complementary approach to LBAs. Hybrid LBA/LC–MS methods combine the advantages of each technology to increase the assay sensitivity and specificity. Traditionally, anti-analyte antibodies are used for immunoaffinity enrichment prior to LC–MS analysis and in the case of protein therapeutics, protease digestion followed by LC–MS analysis of signature peptides. Aptamers are single-stranded RNA and/or DNA molecules with high binding affinity and/or specificity that can be utilized as an alternative to traditional antibodies.

Aptamers can be generated against nearly any analyte through a randomized library screening procedure termed Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Here, we present a case study utilizing an anti-human IgG aptamer to affinity purify human IgG therapeutics for preclinical bioanalysis.

What will you learn?

  • An anti-human IgG aptamer able to replace the traditional anti-human IgG immunoaffinity reagent for hybrid LBA/LC–MS bioanalysis of human IgG therapeutics in preclinical species
  • Aptamers to replace traditional, animal-derived antibody affinity reagents in alignment with EURL ECVAM recommendations (JRC120199)
  • Advantages of aptamers including: easy-to-scale-up production, easy conjugation to functional groups, shorter production time (~3 months), reduced lot-to-lot variability and reduced interference for signature peptide LC–MS analysis

Speaker

Brendan L Powers

Senior Manager, Bioanalytical Chemistry, Labcorp Drug Development (WI, USA)

Brendan L Powers joined Labcorp Drug Development in 2018 and has more than 10 years of experience in biological and analytical research. As a Senior Manager of bioanalysis LC–MS method development, he undertakes original research that includes developing and confirming highly sensitive, reliable assay methodologies for fast and accurate analysis of pharmaceuticals and biopharmaceuticals in biological fluids and tissues. Powers is an author or co-author on more than a dozen peer-reviewed publications and industry presentations, including articles in The Journal of Cell Science and The Journal of Biochemistry and Molecular Cell. He holds a BSc in biochemistry from the University of Illinois (IL, USA) and a PhD in biochemistry from Purdue University (IN, USA).



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