With a focus on advancing personalised cancer treatment, scientists have demonstrated that biomarkers are not enough to tell which patients are likely to respond best to immunotherapy.

According to a study from the University of Bath’s Centre for Therapeutic Innovation (CTI-Bath), clinicians also need to understand how immune cells and tumours are interacting within a patient, rather than relying on the levels of associated proteins present when prescribing the optimum treatment.

The research team – alongside colleagues in Bordeaux – has published the study in the journal Cancers. Results validate a quantitative imaging platform incorporated at CTI-Bath, which can predict whether a cancer patient would respond to immunotherapy treatment.

Cancers typically evade detection by the immune system, making themselves invisible to the natural anti-tumour response and actively blocking it. One type of immunotherapy – immune checkpoint inhibitors – remove the brakes that the tumour has applied to the immune system. This reactivates the natural anti-cancer response, which in turn destroys the tumour.

To investigate the role of these types of the immune checkpoint regulators in cancer patients, the research team recruited 15 patients with metastatic lung tumours who were undergoing a treatment called radiofrequency ablation (RFA). Furthermore, In some cases, treating tumours in one lung using RFA can cause tumours in the other lung to also reduce in size.

Researchers compared levels of the regulators and their targets with how they were interacting – using the immune-FRET molecular imaging platform thatf was developed by Professor Larijani and co-workers in UK and the EU. The technology can establish how molecules interact at a nanoscale level in single cells and tissue samples.

It is the first time these interactions have been quantified within RFA patients and they show that engagement did not correlate with the quantity of protein present. In conclusion, this means that prescribing based on the levels of proteins present is unlikely to be suitable.

Immune responses against factor VIII (FVIII) – used to treat haemophilia A – are influenced by the microenvironment of antigen-presenting cells.

The findings have emerged from a scientific study conducted in partnership between the Institute Krems Bioanalytics of IMC University of Applied Sciences Krems (IMC Krems) and Takeda.

Haemophilia A is a hereditary bleeding disorder caused by the absence or deficiency of active clotting FVIII in the blood. A major complication of this therapy is the development of a neutralising immune reaction in 30% of patients, therefore rendering the administered FVIII ineffective. The research group, led by institute deputy head, Dr Christian Lubich, set out to address the ongoing issue.

During the study, a cell culture model was used to investigate the impact of the microenvironment on factor VIII uptake and processing within antigen-presenting cells. It was discovered that observed alterations in protein processing might have profound effects on immune responses to FVIII.

The novel data provided will form the basis for developing future FVIII therapies that elicit minimal immune responses in patients.

Dr Lubich explained: “The experimental design of our cell culture study aimed at taking a closer look at the response of different immune cells in the context of FVIII administration and thereby gaining better insight into the underlying processes.”

He added: “Immunopetidomics is a pioneering method for investigation of the composition and dynamics of proteins presented by antigen-presenting cells with the aid of mass spectrometry. This method can be used, for example, to determine peptides of a pathogen, a tumour cell or, as in this case, a biotherapeutic agent that elicit an immune response.”

IMC Krems specialises in innovative bioanalytical services and the institute focuses on tailor-made immunogenicity assessments.