List of questions

Do you envision immunscore as a tool in clinical practice and how do you work in Sweden to complement TNM with immunoscoring?
How should immunoscore develop to implement it into clinical practice? –ie is it feasible to go from IHC to NGS or such?

n.a.

QUESTION (AZ): How can industry aid a more equal and fast access to drugs and diagnostics that are not yet available on the market (from your perspective)?
How do you ensure structured registration of biomarkers in the present registers? Is it necessary that biomarkers are already in a register before drugs are made available?
QUESTION(Novartis) :Clinical trial setting in oncology from phase I to phase IV:
a. How can scientists and pathologist in clinical development and diagnostics collaborate more frequent and how can pharma industry support this collaboration?
b. Selected patients in diagnostic setting in the hospital may differ from the patient population selected by the test used in the clinical trial, as different technology can deliver slightly different results. How can scientists, pathologist and pharma work together to validate and standardize the testing (if it is a homebrew or laboratory developed test), ensure that the results are consistent and comparable across other labs in Sweden/countries?
c. In what forum can scientist and pathologist together spread their knowledge to other labs/clinics?
d. Do we need guidelines for validation when it comes to testing with different methods in clinical practice?

n.a.

Q1: What is the significance of the homologous recombinant repair* (HRR) genes for the treatment with PARP inhibitors and the genetic factor, what does the data say?
How will the interpretation of “variants of uncertain significance” affect treatment?
Q2:What is your opinion on the diagnostic alternatives available as a means to decide what treatment a patient should have (specifically for immunotherapy)?
How will you implement immunohistochemistry assessment of PDL1 expression as a diagnostic tool before immunotherapy treatment?
What alternative diagnostic tools do you wish to introduce for stratification of patients to be treated with immunotherapy?

n.a.

What could be clinically feasible biomarkers for endometriosis associated/ chronic pain?

Pain and chronic pain is severe symptom in endometriosis and we would be interested in clinically feasible biomarkers for such pain.

QUESTION (Bioarctic): What new predictive biomarkers are being identified for early Parkinson’s disease?
QUESTION (Mercodia). What is the need for new diagnostic tools for diagnosis/monitoring of neurodegenerative disease, potential biomarkers?

n.a.

How far has the methodology of multiplex IHC come for analysis of several markers at the same time in routine diagnostics?

Use of Multiplex testing IHC in routine diagnostics. Increasing number of biomarkers are needed for routine diagnosis and biopsy material are often in short supply.

What might be the medical benefit with predictive monitoring during cancer treatment (mainly haematological cancer and solid tumours) ?

-Chemoresistance testing and multiplex assays are sometimes questioned with regards to diagnostic efficacy.
-Markers/cells maybe cumbersome to analyze (selection, sensitivity of analysis) for routine use.
-Is there a need for predictive monitoring taken into account the possibilities we have with genetic profiling for personalised treatment?

What is the diagnostic risk of using CTC’s (Circulating Tumour Cells)?

Using CTCs for disease prognosis is an exciting area, since it can be made through a simple bloodsample instead of using biopsis, but are there technical problems of selection?

What are the hurdles transferring unstable biomarkers from a preclinical to a clinical setting?

In a preclinical setting Biomarkers can sometimes be identified and used but fails to transfer to a clinical setting. In cases when this is due to a short half-life, how does the team in a clinical setting work to minimize time from patient to pathologist and diagnosis?

Is there a general standard operating procedure working with risk samples or are samples with confirmed versus unknown disease status handled differently? What are the risks and is there a need for better pathogen inactivating methods?

Is there a risk working with potentially infected patient samples in laboratories? How are they treated to not infect personal?

What can be done to reduce preanalytical errors in point of care testing?

We see a challenge in finger stick sampling and sample processing.

Is there a good biomarker for viral infections?

A lot of people is looking for this but no golden standard exists.

What are the strategies for how to solve antibody cross reactivity in multiplexed assays? Strategies avoiding excessive antibody screening and validations to avoid cost bottlenecks?

To enable biomarker discovery based on biomarker signatures and fast progression to development there is a need for flexible and cost effective assay design.

How can we characterize and describe in quantitative terms the function and integrity of the lung epithelial barrier in health and disease in humans?

The lung epithelia form a tight barrier between the alveolar space and the lung parenchyma, allowing only limited permeability except for agents vital to the respiration such as inhaled and exhaled gases.
This barrier is regionally compromised as one consequence of inflammation or other events in several lung diseases, with COPD and asthma of particular interest to GSK , and this perturbed state may be maintained even after the inflammatory burden has been reduced. It is believed that this aberrant epithelial barrier can be not only a sign of an underlying disease but may also participate in the promotion and maintenance of the tissue pathology.
Normalisation of epithelial function is therefore, in principle, a potential therapeutic approach for lung disease. As a consequence there is a desire to have available tools and biomarkers which can describe the epithelial barrier integrity with a view both to measuring the effects of disease and the benefits of a putative treatement.

What possibilities are there to develop small accurate sensors that detect cannabis in breath?

The need of an easy way to detect cannabis users without blood or urinsample is huge. We have the platform and the application but lack the sensor to detect.

What is the need for new diagnostic tools for diagnosis/monitoring of cardiovascular disease, potential biomarkers?

n.a.

Is there a need for improved GLP-2 assays?

n.a.

QUESTION (Bioarctic): What new predictive biomarkers are being identified for early Parkinson’s disease?
QUESTION (Mercodia). What is the need for new diagnostic tools for diagnosis/monitoring of neurodegenerative disease, potential biomarkers?

n.a.

Clinical trial setting in oncology from phase I to phase IV:How can scientists, pathologist and pharma industry work together regarding setup of new biomarkers for diagnostic testing and testing of drug specific resistance mutations in methods like Next Generation Sequencing, FISH, Immunohistochemistry? What is needed from pharma industry?

QUESTION (AZ): How can industry aid a more equal and fast access to drugs and diagnostics that are not yet available on the market (from your perspective)?
How do you ensure structured registration of biomarkers in the present registers? Is it necessary that biomarkers are already in a register before drugs are made available?
QUESTION(Novartis) :Clinical trial setting in oncology from phase I to phase IV:
a. How can scientists and pathologist in clinical development and diagnostics collaborate more frequent and how can pharma industry support this collaboration?
b. Selected patients in diagnostic setting in the hospital may differ from the patient population selected by the test used in the clinical trial, as different technology can deliver slightly different results. How can scientists, pathologist and pharma work together to validate and standardize the testing (if it is a homebrew or laboratory developed test), ensure that the results are consistent and comparable across other labs in Sweden/countries?
c. In what forum can scientist and pathologist together spread their knowledge to other labs/clinics?
d. Do we need guidelines for validation when it comes to testing with different methods in clinical practice?

n.a.

What would be the most efficient way of finding new (protein) biomarkers for future diagnostics?

NA

What diseases are in urgent need of screening for biomarkers to develop (better) diagnostic tests?

NA

What characteristics are important to a diagnostic test? Are any of these particularly critical? a. Reproducible results b. Accurate quantification c. Detection range that include both healthy and sick levels d. Quick method e. Simple method f. Price g. Other?

NA

Genetic biomarkers predictive of the development of opioid addiction:Are there any known genetic biomarkers for the development of opioid addiction? What do you see the role of genetic biomarkers in managing use of Opiods?

Patients who are prescribed opioids for pain treatment are at risk of developing opioid addiction, and it is hypothesized that different factors, including genes in opioid, pain, and rewarding pathways, will differentiate which patients are more prone to develop opioid dependence.

What are reliable and cost-effective methods for epigenetic biomarker assessment and development and especially, statistical methods that are accepted and validated in this context?

In order to support a preclinical small molecule project, we are interested to at an early stage evaluate potential biomarkers in hematological cancer patients, and especially to map the epigenetic signature of a specific subtype. The overall goal is to (ideally) provide tools to predict the treatment outcome for a specific type of therapy targeting epigenetic mechanisms.

We are looking for analytical situations where heterogeneous interactions of proteins and cells or tissue can be further developed into diagnostic methods. An area of interest is e.g. Fc-interactions with therapeutic antibodies. We would like to discuss problems and possibilities related to such assays and outcome data from protein and cell interaction related assays.

What kind of interactions are of interest to measure?

Interaction Map® is a further development of classical biophysical interaction analysis and can be used to analyze the outcome results from real-time analysis of protein interactions. Basically Interaction Map resolves a binding curve into the underlying interaction processes and can now be used also for diagnostic purposes. We developed Interaction Map as a method to analyze complex protein –cell interactions but it turned out to be very useful also for surface plasmon resonance (SPR) data. It give measures on how much each interaction process contributes to the binding.
LigandTracer® offers a simple and accurate method for detection and quantification of biomolecular/cells interactions in real‐time using labeled biomolecules. Binding curves can generate on‐off rate constants and affinity based on labeled ligands and using different detectors. LigandTracer can further be used to analyze heterogeneous interactions between proteins and tissue sections.

Much more information of potential biological relevance could be generated by our methods simply because real-time information about the interaction process is used.

Q1: How often or important is it to measure glucose/lactate within the intensive care followed by anastomosis/gastrointestinal operations? Is there a problem with unspecific diagnostic tools? Other current problems related to lactate/glucose measurements?
Q2: Is microdialysis a suitable methodology to use within the hospital? Status in terms of research and success rate? In terms of comparison to whole blood analysis?
Q3: Would a continuous measurement of glucose/lactate with microdialysis be of benefit to detect complications related to diabetes? Is there a need of a new screening method than the current tests at 0h and 2h when preforming a glucose tolerance test?

point of care solutions, diagnostic device, biosensor, biomarker discovery & validation

Q1. When measuring antibodies in a direct immunoassay, i.e. detecting specific antibodies towards an antigen by having the antigen bound on the solid phase and detecting the antibodies by isotype specific antibodies, there might be an underestimation of the signals by interfering antibodies of other isotypes. That is, if you are interested in measuring IgE towards antigen X you will have a competition for binding by say for example IgG directed towards the same antigen and you could also have IgG binding to the IgE molecules and thus interfering with the assay. How should a method be set up to accurately measure a specific antibody isotype in light of these issues?

Q2. The ImmunoCAP has a high sensitivity and is thus very good at picking up both high affinity and low affinity IgE. To be able to find out if this hypothesis is right it would be very interesting to have a method that could distinguish between high and low affinity antibodies in a polyclonal serum and also give an indication of the overall distribution in that particular sample. How should this method be set up?

Allergic individuals have IgE specific for certain allergens in their blood. An allergic reaction is triggered by cross-binding of two IgE, bound to a mast cell via the FcR by, an allergen. Therefore there is a diagnostic potential to be able to quantify IgE towards certain allergens or allergen extracts. ImmunoCAP (produced by ThermoFisher Scientific, Phadia) is a fully atomized test that quantifies IgE towards many different (over 600) allergens. Sometimes there is a direct proportion between the levels of specific IgE found in the serum and the severity of the allergy of an individual. But sometimes there is no relation between these two parameters what so ever. Perhaps this is due to a difference in affinity of the specific IgE antibodies