Unlocking the future of antibody-drug conjugates

Labcorp bioanalytical services has supported nearly half of the approved antibody - drug conjugates (ADCs) on market today. Access the on-demand session as we discuss LBA and LC-MS insights gleaned from our deep bioanalytical experience with ADCs, bioanalytical opportunities and challenges we have encountered, how innovative strategies can overcome key issues, and a forward-looking perspective on ADC bioanalytical strategies for this rapidly evolving market.

Labcorp Announces 2024 Third Quarter Results

Updates Full-Year Guidance Results from Continuing Operations for third quarter 2024 versus last year: Revenue: $3.28 billion versus $3.06 billion Diluted EPS: $2.00 versus $2.11 Adjusted EPS: $3.50 versus $3.38 Free Cash Flow: $162 million versus $171 million Updated Full-Year 2024 Guidance:

Impact of implant location on in vivo therapeutic response and immune modulation in the MC38-luc mouse colon carcinoma model

EORTC-NCI-AACR (ENA) Symposium 2024 -- Mouse tumor models play an essential role in investigating tumor biology, evaluating therapeutic response and predicting clinical outcomes. The location of the tumor, whether implanted subcutaneously or orthotopically, can significantly impact its growth, spread and response to treatment. The MC38-luc mouse colon carcinoma model is widely used in preclinical cancer research for studying tumor biology and immunotherapy responses. The aim of this study was to evaluate the antitumor efficacy and immunomodulatory effects of immune checkpoint inhibitors (ICIs) in subcutaneous (SC) and orthotopic (OT) MC38-luc mouse models.

Comparison of manual vs. automated extraction techniques for RCL clinical monitoring

ESGCT 2024 -- Transduced cell therapies, e.g., CAR-T cells, offer a powerful therapeutic strategy for treatment of various cancers and auto-immune diseases. CAR-T and analogous therapies are often transduced using lentiviral vectors to integrate the chimeric antigen receptor (CAR) construct into the cell line. The use of lentiviral vectors introduces the risk of patient exposure, with a particular concern regarding replication competent lentivirus (RCL). In addition to RCL testing during cell product release, there is a necessity to establish the absence of RCL over the course of clinical studies assessing lentiviral-transduced cell therapy products. The current FDA recommendation for clinical monitoring is for testing of blood/PBMCs for the absence of RCL before dosing and, periodically over the course of at least the first year following dosing. In addition to target-specific transduced cell therapy vector copy number (VCN) method development and validation, Labcorp supports RCL testing for clinical samples with a validated VSV-G envelope protein targeting qPCR method. Recent further validation work has refined the previously manual whole blood extraction method to an automated process using half the sample input and aligning with extractions supporting VCN analyses.

Receptor occupancy assay development challenges for rare targets of bispecific drugs

AAPS PharmSci360 2024 -- Receptor occupancy (RO) assays allow for the quantification of binding of therapeutics to their intended targets on the surface of different cell subsets. Flow cytometry-based RO assays are a strong tool for preclinical and clinical development, providing rapid, high-throughput and quantitative measure for PK/PD modelling. Research challenges remain however when RO assays are developed and validated for rare low expressing targets. Herein we present an example of such an assay, its challenges, and the steps taken to resolve performance issues with impact on data and RO calculations.

Validation of a quantitative PCR (qPCR) assay for the detection and quantification of replication competent lentivirus for patient monitoring in lentiviral vector-based cell therapy studies

AAPS PharmSci360 2024 -- Lentiviral vectors are a common delivery system for various cell therapies, such as CAR/TCR-T cell therapies. There is a potential risk for replication competent lentivirus (RCL) in patients receiving lentiviral vector-based cell therapies. There is a critical need for regular RCL monitoring in patients. PCR-based assays for RCL detection are recommended by the FDA. Our objective was to validate a qPCR assay based on quantification of vesicular stomatitis virus glycoprotein (VSV-G) envelope protein gene sequence for RCL.

Alternative approaches to animal testing for ecotoxicity assessments: Validating the OECD319 regulations

SETAC North America 2024 -- Fish bioconcentration studies are carried out to determine whether substances have the potential to bioaccumulate or to bio-magnify throughout different trophic levels. As the requirements to conduct these studies on a broad variety of industrial chemicals, pharmaceuticals and crop protection products increase across the globe, so does the numbers of fish needed to fulfil these investigations. Prior to the revision to the OECD Test Guideline (OECD 305: 2012), the preferred method of testing required three doses of chemical (including a control) with up to 100 fish per dose. Latterly, there is now the option to test on one concentration and the control only, providing there is scientific justification. This has the potential to decrease the numbers of fish used in these tests by one third (100 fish per study). Here we present our approach to assess the selection of positive controls to be used in these assays using pyrene, the reference chemical stated in the guidelines, together with testosterone and diclofenac as both undergo Phase I hydroxylation reactions in the presence of S9 and hepatocytes, similar to pyrene.

Per- and polyfluoroalkyl substances (PFAS): Validation of methodology for the determination of residues in fruit, fruit processed commodities and fish tissues

SETAC North America 2024 -- Per- and polyfluoroalkyl substances (PFAS) are a class of synthetic organofluorine compounds that have become a concern due to their persistence in the environment following extensive use over the last few decades. Due to their high degree of chemical stability as well as their widespread use, PFAS compounds are increasingly being detected in the environment and appear to persist for extended periods of time. Furthermore, exposure to these chemicals in everyday objects such as packaging and cookware, as well as within certain areas of industry, has led to the apparent bioaccumulation in certain areas of the population. Because of the concerns over health and environmental issues associated with PFAS chemicals, there has been a need to be able to monitor the occurrence of these materials in food commodities. The work described in this poster was a project to develop and validate an LC-MS/MS method for the analysis of a “typical” suite of PFAS analytes in fruit (strawberries and grapes), fruit processed commodities (jam and wine) as well as in fish tissues (edible muscle fillet). A simple and robust method was required, that could be easily applied to routine analysis at low concentrations, using commonly available equipment and approaches.

Enabling gene therapy access: Labcorp's first cell-based companion diagnostic (CDx)

The emergence of novel gene therapies has necessitated the development of cell-based CDx assays, posing multiple technical and operational challenges. Labcorp worked with a sponsor to develop the nAbCyte™ CDx assay to determine patient eligibility for a novel gene therapy program BEQVEZ™ (fidanacogene elaparvovec). nAbCyte is an FDA-approved in vitro CDx device that detects neutralizing antibodies to the AAVRh74var capsid in serum specimens from patients previously diagnosed with hemophilia B. This case study illustrates how Labcorp worked with the client and regulatory agencies to overcome development hurdles with a customized approach combining scientific expertise, collaboration, strategic engagement and governance.

Navigating the complexities of the Biocidal Products Regulation

Biocidal products are used to control unwanted organisms (e.g., pests, such as rats, or micro-organisms, like bacteria) that are harmful to the health of humans, animals or the environment. They play an important role in everyday life and are regulated in the European Union (EU) and European Economic Area (EEA) by the European Chemicals Agency (ECHA). A biocidal product must be authorized before it can be placed on the market, although exemptions apply for active substances included within ECHA’s Review Programme.