Immuno-oncology (IO) relates to cancer treatments that use immune regulation. This extremely promising therapeutic method is of particular interest for cancers that demonstrate high resistance to cytotoxic drugs.
IO makes use of the potential that the immune system can recognize and respond to tumor-associated antigens. Research is in progress with a variety of therapeutic modalities, such as vaccines, monoclonal antibodies, bispecific antibodies, recombinant cytokines and autologous and allogeneic T cells and NK cells.
Effective and successful trials rely on accurate techniques that expose the responses of the tumor cells and the immune system, irrespective of the IO treatment. It is also critical to evaluate what the genome of the patient and the tumor can reveal about the leading treatment approach and prognosis.
Cerba Research’s global central laboratory possesses competent levels of expertise and technology to display the impact of the complete range of IO approaches. With over 50% of clinical trials focused on oncology, Cerba Research’s clinical and technology experts have acquired a vast amount of first-hand experience in:
- Genetic profiling predicated on cell, tissue and body fluid samples, such as liquid biopsies, with techniques that include quantitative real-time and digital PCR, microarrays and next-gen sequencing
- Circulating biomarker detection and identification, with methodologies such as ELISA and numerous single and multiplex automated immunoassays
- Cell work, which includes bespoke flow cytometry panels for determining general immune responses and evaluating the efficacy of antibody- and CAR-T cell-based therapies, cell enrichment and PBMC preparation
- Tissue work, such as tissue prep, staining, IHC and multiplex IHC for evaluating in situ immune cell infiltrates, digital pathology and ISH
As IO-focused projects are extremely challenging and sometimes exploratory, Cerba often works closely together with its clients’ scientists to design custom-made solutions. Cerba Research is ready to advise clients on how to receive bespoke support for their projects.
Interpreting gene expression
Gene expression can reveal an elaborate account concerning the biological response to a drug or cancer, but it requires an extensive range of techniques to understand it. Cerba Research offers a complete range of powerful modern methods for reading and interpreting gene expression by exceeding the basic quantitative RTPCR and PCR requirements.
Scores of genes with a reported impact on myeloid malignancies and solid tumors can be assayed with Cerba’s off-the-shelf sequencing panels and whole exome and genome (WES/WGS) next-generation sequencing (NGS) solutions.
Copy number variation (CNV) and rare events can be identified with extremely sensitive digital PCR assays.
Cerba Research’s sequencing methods facilitate the identification of tumor mutation burden (TMB), determination of neoantigens, quantification of CAR-T cells and the discovery of new RNA/WDNA biomarker signatures.
From whole exome sequencing to targeted MSI status identification and miRNA sequencing, Cerba’s experts can design and validate novel assays and interpret the results with great proficiency.
Cerba Research will provide the answers hiding in samples using cutting-edge platforms for genome work to guarantee reliable and reproducible results from each sample:
- Affymetrix® Cytoscan® HD for SNP detection
- Bio-Rad® CFX384™ for real-time PCR
- Bio-Rad® QX100™ for digital PCR
- Bio-Rad® qPCR Chip panel for verification of tumor microenvironment
- Illumina® MiSeqDX®, NextSeq® 500, HiSeq®1500, and NovaSeq® 6000 for sequencing
Case study
Phase I/II of a new type of antibody targeting CD70 to establish the biological range of solid tumors and hematological malignancies
Cerba Research’s solution
Developed and validated a quantitative RT-PCR assay to measure CD70 levels accurately in liquid biopsy samples (whole blood).
Revealing circulating biomarker profiles
Circulating biomarkers have warranted the attention paid to them since their discovery, granting scientists with novel diagnostic and prognostic insights into diseases.
A range of biomarkers have shown to be useful in IO, from the established to the exploratory: well-known hematology parameters, such as absolute lymphocyte counts; biochemical parameters, including β2-microglobulin and LDH; and cytokines and chemokines, which still have significant potential to reveal.
Cerba Research can provide a complete range of methods for establishing, evaluating and monitoring circulating biomarkers, including methods ideally suited for supplying reliable results across the length of demanding long-term studies.
For advanced exploratory biomarkers, Cerba’s expert scientific team has developed a rapid, fit-for-purpose and dependable pre-validation protocol that reveals which solution is perfectly suited to the needs of the study.
Cerba then brings this to full validation to make sure the best support is offered for all collaborative R&D programs and clinical trials.
To release their full potential as inclusion/exclusion and monitoring tools, Cerba Research’s experts have applied this development approach to generate a range of off-the-shelf biomarker assays, each running on the most suitable instrument:
- Ella Protein Simple System
- ELISA platform
- LC-MS/MS
- Magpix Luminex
- MSD® S600 Meso Scale Discoveries
- Quanterix Simoa HD1
Example
Assay type: V-PLEX immunoassays on the MSD® S600 have:
- High dynamic range for measurement across the spectrum from healthy to sick
- High sensitivity and lot-to-lot consistency
Our clinical trial-ready system:
- Facilitates high-throughput, single-well multiplexing with low sample volume
- Has been validated on human serum and plasma
- Has established sensitivities and stabilities
- Provides comprehensive panels of chemokines, cytokines and pro-inflammatory and angiogenesis markers
Investigating immune cell subpopulations
Flow cytometry (FCM) facilitates rapid and complex phenotyping without affecting sensitivity. It reports characteristics of cell subpopulations with excellent sensitivity, even with frequencies as low as 1:10,000.
Results can be specified as percentages, absolute cell counts or the total number of molecules per cell.
Utilizing a global and coordinated network of leading laboratories and possessing more than 25 years of experience with FCM analyses, Cerba Research can call on this dynamic technology in various ways to support IO studies.
Cerba Research has developed immunophenotyping panels for both peripheral blood and bone marrow aspirates, which are appropriate for patient follow-up and for evaluating recovery and remission in clinical trials that target leukemia, lymphoma and myeloma.
In trials that include biopharmaceuticals, FCM is essential for immune monitoring and the precision evaluation of pharmacodynamics/receptor occupancy (PD/RO).
Cerba Research is delighted to offer a range of panels determining T cell phenotypes (naive/memory, activation stages, T-helper subsets and regulatory T cells), B cells, NK(T) cells, dendritic cells, basophils, macrophages and monocytes, neutrophils and MDSCs.
Employing global standardization procedures and acceptance criteria on 8- and 10-color advanced equipment, Cerba Research guarantees the consistency and reproducibility of results.
As with general testing, the sample workflow is completely integrated into Cerba’s Clinical Trial Management System (CTMS), ensuring secure data transfer along the entire workflow, from test request to reporting.
Case study
First-in-human clinical safety and efficacy trial for CAR-T cell treatment for B-ALL
Cerba Research’s solution
Designed and validated pharmacokinetics FCM assay that uses an anti-idiotype antibody specific for the CAR-T cells used in the trial - tracks the immunophenotype, expansion and persistence of the CAR-T cells in the circulation of the patient.
Case study
Clinical efficacy trial for a monoclonal antibody that targets an epitope strongly expressed on leukemic cells
Cerba Research’s solution
Designed and validated receptor occupancy qFCM assay with calibration beads executed at the same time as the clinical sample. It measures drug-to-target binding and generates robust pharmacodynamic data.
Delving into tumor biomarkers and behavior
Next-generation histo-cytopathology has expanded the potential for understanding tumor biology. In the context of IO, Cerba Research takes this approach to detect tumor biomarkers from patient biopsies and to represent the tumor environment and its infiltration by immune cells, supporting:
- Correlation of target presence and disease evolution
- Inclusion/exclusion decisions
- Monitoring of immune response during treatment
- Patient stratification
To make sure a complete exploration of tumors is conducted, Cerba Research’s experts have managed to gain proficiency across an extensive range of techniques relevant for successful application of next-generation histo-cytopathology, including (IHC), in situ hybridization (ISH) and tissue microarrays.
Cerba Research used the appropriate, world-leading platform for each technique, including the Ventana® BenchMark® XT/Ultra, Leica® Bond III/RX, and Dako® Link 48, along with Leica® and Hamamatsu® digital imaging platforms.
Cerba also works in collaboration with a global network of experts and clients’ in-house scientists to make sure that trial results are characterized as necessary.
Case study
Multiple myeloma trial centered around anti-CD138 antibody treatment
Cerba Research’s solution
Cerba developed an extensive portfolio of IHC (CD138 staining) and FISH testing to assess complete response and very good partial response (CR+VGPR) rates - results suitable for patient stratification.
Cerba Research can also provide a combined multiplex immunohistochemistry and digital pathology approach that facilitates interactions between a target and numerous receptors and/or ligands to be evaluated and ensures no operator bias effects throughout image analysis.
This approach utilizes PerkinElmer’s advanced Vectra® Polaris™ Automated Quantitative Pathology Imaging System, which facilitates the study of up to 8 markers on one slide.
Cerba Research can readily support the development and validation of protocols for new biomarkers, even for multiplex and complex staining. The typical time frame is just a few weeks, and Cerba Research is constantly expanding its portfolio to match the active developments in IO research.
Cerba Research: A global network of experts
Cerba Research’s global central laboratory network possesses expertise that extends five continents, offering bespoke solutions to assist in the success of its clients’ clinical trials.
As a division of Cerba HealthCare, a European leader in clinical pathology, Cerba Research is dedicated to enhancing the understanding of disease and the quality of treatment. At Cerba Research, there is a strong belief in the added value of having experts moored in real-life practice analyzing your samples.
All of Cerba’s affiliate laboratories have their regular activities but also render and discuss results with community hospitals and physicians, making sure the highest quality interpretation of complex clinical and safety data.
Clinical trials are also present unique opportunities to design new tests and technologies that have yet to reach the clinic.
Cerba Research has assembled a consistent network of expert laboratories specialized in key aspects of modern-day R&D challenges, including circulating cell-free DNA detection, lncRNA sequencing and multiplex IHC and scoring.
Throughout Cerba Research’s entire network of scientists, clinical experts and physicians, clients are guaranteed the successful coordination of communication and activities. All Cerba scientists possess a high level of competency as well as proficient academic and laboratory experience, combined with complementary backgrounds in pharmaceutical, biomedical and biotechnological sciences.
Cerba Research is able to make clients’ IO studies a success. Clients can rely on Cerba Research to discuss the details of even the most challenging projects, translating scientists’ needs into concrete solutions.
Image Credit: Cerba Research
About Cerba Research
For over 35 years, Cerba Research has been setting the industry standard for exemplary clinical trial conduct. Today, across five continents, with a focus on precision medicine, we are changing the paradigm of the central lab’s role in complex clinical research.
From protocol inception through development and to market, our passionate experts deliver the highest quality specialized and personalized laboratory and diagnostic solutions. Partner with us for the most efficient strategy to actualize your biotech and pharmaceutical products sooner and improve the lives of patients worldwide.
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