The Antibody final meeting in September will conclude a several year-long research venture aimed to increase the understanding of how monoclonal antibodies behave at high concentrations – with the hope to enable more effective treatments of for example cancer.

Anna Stradner leads the work in the Antobody program.

– I am so proud that we are finally at this point, where we are able to share our concerted results. Our approach to work with one antibody, under well-defined conditions, to create a huge reference data set has proved very successful, says Professor Anna Stradner, Professor in Physical Chemistry at Lund University, and Antibodies in Solution programme leader.

She emphazises that the programme is an example and a showcase of what can be achieved in a bottom-up action of scientists that are interested in advancing understanding of an important system, in this case monoclonal antibodies, that is much too complex to be understood using a limited set of methods.

– It also shows the important role that LINXS can play in such a context: LINXS has initially brought together key actors, it helped to define the most important needs and deficiencies of the community and its knowledge, and in a next step it provided an environment where this bottom-up action could develop and grow, says Anna Stradner.

Monoclonal antibodies increasingly used in cancer treatments

Monoclonal antibodies – clones of human antibodies that are made in the laboratory – can stimulate the immune system, and are thus increasingly used by pharmaceutical industry for example for cancer treatments. They can for example block the connection between a cancer cell and proteins that promote cell growth, which is necessary for cancer to spread. The aim is for the patient to administer the treatment at home, yet a big challenge is that the antibodies need to be used in very high concentrations to be physiologically effective – making the solution thick, and often very painful to inject.

Aim to gather knowledge on how antibodies behave at higher concentrations

The Antibodies in Solution programme, which gathers 14 research groups, the American National Institute of Standards and Technology (NIST), and the pharmaceutical company Novartis in Switzerland, has aimed to gather fundamental basic knowledge on how antibodies behave at higher concentrations. This knowledge can help the pharmaceutical industry to decide what antibodies they should use and how to formulate them to produce therapies that are easier to inject and administer for patients. Key to their work has been the approach to only work with one reference antibody under identical sample conditions to create a huge data set, of use to both the experimental research groups and the modelers within the programme.

Scientific illustration. Photo and illustration.

– By being a large consortium, we have been able to make substantial progress. It is not enough to apply one or two or three methods, you really need a concerted effort. By using the same antibody, we can compare and triangulate results – which is impossible if you do one experiment on one antibody, and the other experiment on a different antibody, or on the same antibody under slightly different conditions, says Anna Stradner.

Experiments to elucidate and predict antibody behavior

The different research groups have performed X-ray, neutron, and light scattering experiments and applied various complementary techniques covering a huge range of length and time scales to gain more knowledge on antibody flow behavior, interactions between antibodies and antibody stability. The consortium has also been producing theoretical models to predict antibody behavior under various solution conditions. Here the specific structure of antibodies, which is Y-shaped, has added another level of complexity to their work.

– The goal has been to reach a level of understanding where you can make predictions from the molecular structure of a single antibody without having to go through the elaborate production steps involved in finding out how it will behave at high concentrations, which is both time consuming and very expensive, says Anna Stradner.

She continues:

– Our results can be of great use for pharmaceutical industry as they are developing new treatments, since they can predict important knowledge on flow behaviour, solution stability and turbidity of antibodies in solution.

The antibody final meeting: a time for both closure and new beginnings

Anna Stradner is now looking forward to discuss the consortium’s results and their implications at the upcoming final Antibody meeting in September, including from an industrial viewpoint – both with consortium members and other researchers.

The event will comprise both presentations and interaction, including a round-table discussion at the end. Anna Stradner notes that she is very much looking forward to the outcomes of these discussions.

– I hope to see many questions from people outside our consortium. They might think about things we have completely missed, and bring a fresh view. I also expect that it will show still existing gaps in our understanding, and it will hopefully also lead to in-depth discussions of future steps beyond the program.

– We will also discuss how to make our experimental data and the modeling and analysis programs available for the community. At the end, the intention of our program was always to create a true reference data set that can be used not only by the consortium members but by the international community for future work. We also hope that the meeting will inspire other people to launch similar bottom-up actions and utilize LINXS for this purpose.

She is also curious to see if the meeting might spark new collaboration and approaches to the area.

– We certainly want to continue since our work is by no means finished! Discussing how, and in what format will be a big part of the roundtable discussions!