Review: The Future of Biomarkers in Immuno-Oncology

future biomarkers immuno oncology lymphocytes

Immuno-oncology is a Biotech field that is more than just hype – it could solve one of humanity’s biggest health challenges: Cancer.

Bernhard Sixt, CEO ImmunID
Bernhard Sixt, CEO of ImmunID (Source: ImmunID)


In order to bring more effective treatments with fewer side-effects, Biomarkers will play a key role. I wanted to get an expert view on the subject, so I called Bernhard Sixt, CEO of the French Biotech ImmunID, to get a better perspective on this fresh and promising field.

You have 300 billion Lymphotcyes in your body, why wouldn’t you use the power of all of them instead of designing one single drug?!”

That’s basically what Immuno-Oncology is about. Tumor cells are able to block the immune system. The goal of this new generation of drugs is to therefore re-educate your immune system to overcome cancer, and this means targeting specific mechanisms/immune checkpoints of anti-tumor immune response.

Three Immuno-oncology monoclonal antibodies are already on the market (two from BMS, one from Merck & Co.). HOwever, many novel mAbs are in development, as Genentech’s positive Phase II results show.

One could initially think that these therapies work when the target is expressed in the tumor (i.e. PD-L1 for anti-PD-1 drugs), but the real challenge is to first fix the low predictability or whether the treatment will be efficient or not. Results at American Society of Clinical Oncology showed significant activity, even in checkpoint negative patients.

The second challenge is that tumor tissues have to be analyzed to look for expression of targets. Tumor tissues are very difficult to obtain and can be very heterogenious (diverse in content and type). And as Sixt said: “getting the proper tissue is a nightmare“.

Biomarker discovery for combination immunotherapy and proposed new concepts to combat cancer (Source: Melero et al. (2015) Nature Reviews Cancer 15, 457–472, doi:10.1038/nrc3973)

Checkpoints are not the only factor, the activation of the immune system before the treatment plays a crucial role“.

That’s were the future of immuno-oncology biomarkers could be. You could profile the immune system of a patient to find out if he will respond well to the treatment – But how does this work?

It starts with a sample of the patient’s blood, which is much easier to get than a tissue biopsy. You isolate the lymphocytes and analyze the diversity of the T-cell receptor.

After interpretation of the data, you get all the rearrangements of genes possible inside T-Lymphocytes. They are called the V-J rearrangement family and there are around 276 possibilities.

Sixt added: “This gives you an helicopter view and basically defines the immune response.”

‘Helicopter View’ when mapping of T-Cell genetic variation – (Source: Atreca)

Three diagnostic companies are active in this emerging field. ImmunID, Sixt’s company based in Grenoble (France), Adaptive Biotechnologies in Seattle (US) and iRepertoire in Huntsville, Alabama (US). The two leading biotechs here though are ImmunID and Adaptive – so let’s compare them.

The major different here is the type of technology used to do the profiling.

Adaptive uses standard multiplex PCR + Next generation sequencing, whereas ImmunID uses 23 specific multi-N-plex real-time PCR reactions (and lab-on-a-chip microfluidic detection). This translates into a difference in the time needed to run the test.

Secondly, a major disparity between the two biotechs is the field experience.

ImmunID was founded in 2005, and Adaptive in 2009. Both companies provide central testing services for indications other than immune checkpoint inhibitor prediction, but ImmunID has already a CE-marked clinical test.

The third and more salient difference is of course, Finance.

Adaptive is one of the Biotech companies on the planet that has raised the biggest amount of private money: $425M (€393M) – only Moderna and Intarcia have raised more than this. In comparison, ImmunID only raised $13M (€12M) so far.

Data of the 8 billion dollar healthcare startups – (Source: Wall Street Journal)

I wondered why?

Let’s say ImmunID is French and Adaptive is American. It’s amazing how Europe is much more conservative when it comes to Biotech founding“.

Adaptive was founded by a former hedge fund manager, which likely helped him lead these massive investment rounds. This give them much more financial power to develop the technology and reach the market.

However, ImmunID’s test is already marketed in Europe, but it hasn’t been proven for immuno-oncology yet, although, the test can also be used by physicians to view and monitor the immune system of patients while giving a treatment. Physicians are able to better treat their patients, and it helps ImmunID obtain precious data for future development.

The Holy Grail is to have a biomarker in Immuno-Oncology. We are actively working on clinically proving that our technology works…and we already demonstrated strong predictive power for immuno-oncology drugs”.

ImmunID is therefore working with Pharma/Biotech partners to develop the test. “It takes time to find the right partner but we are already in advanced discussion“.

So, in tynig things up, Sixt gave me his view on Cancer: “Immuno-Oncology is extremely exciting. It has already shown good results but it needs better biomarkers to move to the next level. Ultimately, in combining both, we will be able to tackle cancer on a long-term basis by using what evolution has created over million of years: our powerful immune system.”


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