E!10054 Development of a new platform technology for efficient, fast and cost-effective antibody generation

Monoclonal antibodies (mAbs) have become an important source for drug development and diagnostics. Therapeutic mAbs work through a number of mechanisms, such as blocking important signalling pathways. The main goal of the project has been to develop a platform for selection, characterization, and production of mAbs. The EffiBody platform will be more reliable, faster and more cost-effective than current methods. Current development and production of new mAbs is expensive and time-consuming and less reliable; only half of commercial used mAbs recognize the correct target. The new platform developed in this project integrates LC-MS / MS, NGS and bioinformatics tools, in a platform that represents a significant improvement over the current method. The platform facilitates rapid selection of target-specific mAbs, rather than current labour-intensive methods for cell isolation and clone detection. By incorporating bioinformatics tools one can reduce the number of immunization experiments and thus reduce the resource use. Bioinformatics tools are based on data mining and allow interpretation of complex genome and protein profiles related to the selection of antibodies. With the help of the Effibody platform, it will be possible to efficiently, fast, and cost-effectively characterize, select and produce specific mAb. The developed bioinformatics tools will be offered as part of the platform, but in addition, have a significant potential for future spin-out products. The consortium has so far developed various potentially therapeutic mAbs for prostate cancer.

Through this project, we have developed a set of new algorithms and data mining tools, primarily towards antibody development and selection. Regardless of the antibody focus, we believe that there are many generic components from these developments that will prove valuable for biomedical research challenges in general. We especially see the use for these components in our ongoing product development focusing on personalized medicine. This EFFIBODY platform represents a unique tool for future development of both therapeutic and diagnostic antibodies and can be applied in both drug development and basic research, thus having a substantial market potential for all the partners involved. It is obvious that the developed platform for speeding up antibody development will have a major impact on drug development, personal health and on society at large. Through this project, PubGene also has strengthened its global reach through new collaborations.

In life sciences industry, the use of mAbs has become a very important source of pharmaceuticals and diagnostics. Therapeutic mAbs act through a number of mechanisms, such as blocking or modulating crucial disease pathways. For this purpose, mAbs act on specific targets, e.g. cancer cell-specific, to induce immunological responses to cancer cells. The major challenge is that for each target, an individual mAb needs to be produced that has high affinity to the binding site and to avoid cross-reactivity with other proteins. A number of high quality mAbs are on the market, showing high potential. However, currently used methods for mAb production have significant limitations. Resulting mAbs often show low affinity to the target. This can result in partial blocking and will hamper the therapeutic outcome. Another limitation is cross-reactivity as a result of low specificity. Thus, mAbs can block more targets than actual desired which can lead to irreversible damage. Also, mAb generation methods are expensive and time-consuming. EffiBody will develop a new platform technology for mAb production, including new bioinformatics tools, using an entirely new approach that combines mass spectrometry (LC-MS/MS) and next generation sequencing (NGS). Specific advantages will be that high-affinity target-specific mAbs can be easily identified and isolated as LC-MS/MS provides the sequence of the highest affinity binding mAb. NGS creates a reference sequence of the whole immune response. High confidence sequence matches of mAbs are obtained by overlaying the protein and the cDNA sequences. Paired sequences are expressed as recombinant mAbs. The platform technology will be commercialized by MQT, offered as a service. Proof of Concept will be delivered by producing new therapeutic mAbs against newly identified targets. ibiomics and PubGene will develop the bioinformatics tools, which can also be used for spin-off applications.