CT scans are used to view a receeding tumour

A hindrance to future discoveries?

Personalised medicine is a key focus in the development of global healthcare systems. European scientists working on the creation of an individual injection to help cure B-cell lymphoma secured financial backing from EuroNanoMed II, an ERA-Net funding programme under FP7. Yet despite initial progress, the project is now in jeopardy following fresh difficulties in obtaining funding, leaving project co-ordinator Dr Maurizio Bendandi very sceptical regarding future EU research and innovation framework programmes.

Can you briefly explain the background to the Nanovaxid project and the latest developments in your investigation on developing an idiotypic vaccination?

The idiotypic vaccination for lymphoma is based on the fact that most B-cell lymphoma (in particular, nearly all cases of follicular lymphoma, an indolent and yet haematological malignancy) are made of clonal cells expressing on their surface an antibody molecule. This antibody molecule, which differs from patient to patient, contains a portion, termed ‘idiotype’, which is virtually impossible to find on any other antibody from any other patient (even with the same diagnosis), no matter whether we talk about cancer or normal cells.

The good news is that if want to use the idiotype as a vaccine target, any immune response we may elicit against it will only kill tumour cells, while normal cells will be inherently spared. This translates into the lack of any side effects, irrespective of whether the vaccination succeeds or not, eliciting an immune response. The bad news is that being the idiotype, a tumour (and also patient) specific target, we have to produce a different vaccine for each patient. Since the idiotype, per se, would not stimulate the patient’s immune system (which already ‘knows’ it and ignores it all too well), we have to add other components (e.g. immunologic adjuvants) to the vaccine formula in order to improve the vaccine’s potency.

The most used of such adjuvants, called KLH, has shown over the last 20 years to be able to make the vaccine work in about half of the patients treated. The Nanovaxid project was designed to replace KLH with a novel RNA adjuvant and to target the patient’s immune system through nanoparticles after encouraging, preliminary, preclinical data in mice.

How vital has EU funding (through EuroNanoMed, and subsequently through FP7) been to your research?

At the beginning, dealing with nanoparticles and RNA adjuvant molecules, EuroNanoMed seemed tailor-made for our endeavours, particularly given the fact that FP7 tends to fund less risky, more-developed research efforts. Moreover, since other groups have not been as successful with idiotypic vaccinations as we have, many reviewers have grown sceptical in terms of novelty on the one hand and success chances on the other. This is mostly unfair, but we have to deal with the most recent facts.

A recent FP7 application of ours passed the first, but not the second stage of the evaluation. For EuroNanoMed, we joined three dedicated expert partners from Germany, Poland and Spain and successfully applied for funding, but soon found that the devil is in the detail and that this type of project funding, contrary to the FP7, is far less sensible and far more susceptible to national, contingent situations.

From the very beginning, it was made clear that each national agency would finance its corresponding group very unevenly. In Germany, a grant of over €1m was made to its EuroNanoMed partner, Poland awarded about €600,000, while Spain would not commit more than €250,000, despite being the overall project co-ordinator. Even worse, once our consortium’s finance application had succeeded, the Spanish agency enforced further national budget cuts, approving only €160,000 (€32,000 being for indirect costs).

At that point, we realised that we could conduct the mandatory preclinical testing of the new vaccine formulation, but had no money to launch a small follow-up phase I clinical trial. The German partner unsuccessfully attempted to shift clinical grade vaccine production from Spain to a subcontracting company in Germany, but failed to reach an agreement. Consequently, we have been running preclinical experiments producing exciting results, but the clinical development has already been cancelled and the whole project is in jeopardy.

To what extent do you believe the changes introduced under Horizon 2020 adequately address the key issues facing European society, particularly regarding health?

After this negative experience, I believe far less in the EU science financing models and I am very sceptical about Horizon 2020. For me, framework programme grants are too complicated to obtain and there is too little accountability, transparency and review. When you apply for a R01 grant from the National Institutes of Health in the United States, you know in advance who sits on the reviewing panel. I doubt that Horizon 2020 will resolve any of the problems we have experienced so far. I believe the EU should stop relying on experts that, suffocated by a bureaucratic style of acting and thinking, seem to be unable to think out of the box.

Dr Maurizio Bendandi

University of Navarra