Development of novel biomarkers for use in clinical trials

Development of novel biomarkers at Fraunhofer ITEM
© Fraunhofer ITEM, Ralf Mohr

Biomarkers are distinct biological characteristics that can be objectively measured. From a medical point of view, they are indicators of a normal biological or a pathological process in the organism. In medicine, cells, genes, gene products, or certain molecules such as enzymes or hormones, but also complex organ functions or characteristic alterations in biological structures may serve as biomarkers.

Biomarker analysis can be very useful in the development of new drugs. For example, it can enable assessment of the toxic potential of a pharmaceutical, but also of its efficacy. Measurements of biomarkers are also used to describe the course of a disease or the underlying pathological mechanism, or to predict the outcome of therapeutic interventions. However, the development of biomarkers with sufficient predictive value, i.e. sensitivity, is a huge challenge.

The scientists of the Fraunhofer ITEM Department of Biomarker Analysis and Development have taken on this challenge. In close collaboration with their clinical partners at the CRC Hannover, they develop and analyze novel biomarkers. They have access not only to a large biobank containing tissue and blood samples, but also to patient samples collected during clinical trials. These samples may originate from clinical challenge models after pro-inflammatory inhalation challenge with lipopolysaccharides, ozone, ultrafine particles, or allergens, in some cases also from clinical drug trials. In addition, the scientists also use well-characterized samples from patients with respiratory diseases such as COPD, asthma, pulmonary fibrosis, or allergic conditions such as rhinitis. Depending on the particular target, the scientists use samples from peripheral blood, induced sputum, bronchoalveolar lavage (BAL), or exhaled breath and prepare them for measurement of the biomarkers of interest. In addition to special sample preparation, they also test the sample material for purity and stability, thereby controlling its quality.

Measurements at the protein level performed by ELISA (enzyme-linked immunosorbent assay)

© Fraunhofer ITEM

At Fraunhofer ITEM, measurements at the protein level can be performed by ELISA (enzyme-linked immunosorbent assay) in multiplex systems (Mesoscale Discoveries, MSD) to determine cytokine and chemokine concentrations in the biological fluid under investigation. Analysis of cellular functions or of surface marker expression in cells from BAL, sputum, or peripheral blood by flow or chip-based cytometry provides a good possibility for highly detailed description of cellular interactions or functionalities of subpopulations, both directly and after cell culture. The composition of cells obtained from the patient sample enables important conclusions on the patient’s clinical status or underlying pathomechanisms. All work is performed and controlled in compliance with the quality criteria defined in the GCLP guidelines – guaranteeing correctness of the measurements performed.

Biomarkers in sputum of patients with chronic obstructive pulmonary disease (COPD)

© Fraunhofer ITEM

Cytokine and chemokine measurement to describe inflammatory conditions and determine the disease prognosis is often used in clinical practice to assess the effect of therapeutic intervention. An essential precondition for the use of biomarkers in clinical trials is their correct and reproducible measurement in the available sample material (matrix).

The validity of measurements of a broad range of biomarkers in samples from the lungs of patients with chronic obstructive pulmonary disease – including BAL, biopsies, induced sputum, and serum – was investigated at Fraunhofer ITEM. Because of the large number of variability and reproducibility measurements, it was possible to assess what biomarkers are suitable for analysis in the different matrices investigated.


  1. Inter- and intrasubject variability of the inflammatory response to segmental endotoxin challenge in healthy volunteers.
    Holz O, Tan L, Schaumann F, Müller M, Scholl D, Hidi R, McLeod A, Krug N, Hohlfeld JM. Pulm Pharmacol Ther. 2015 Dec; 35: 50-9. doi: 10.1016/j.pupt.2015.10.011. Epub 2015 Nov 10. PubMed PMID: 26545873.
  2.  Repeatability of and relationship between potential COPD biomarkers in bronchoalveolar lavage, bronchial biopsies, serum, and induced sputum.
    Röpcke S, Holz O, Lauer G, Müller M, Rittinghausen S, Ernst P, Lahu G, Elmlinger M, Krug N, Hohlfeld JM. PLoS One. 2012; 7(10): e46207. doi: 10.1371/journal.pone.0046207. Epub 2012 Oct 4. PubMed PMID: 23056262; PubMed Central PMCID: PMC3464239.
  3. Impact of endobronchial allergen provocation on macrophage phenotype in asthmatics.
    Winkler C, Witte L, Moraw N, Faulenbach C, Müller M, Holz O, Schaumann F, Hohlfeld JM. BMC Immunol. 2014 Mar 10; 15: 12. doi: 10.1186/1471-2172-15-12. PubMed PMID: 24612750; PubMed Central PMCID: PMC4007705.


Meike Müller

Contact Press / Media

Dr. Meike Müller

Head of Department of Biomarker Analysis and Development

Phone +49 511 5350-8144