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

Monoklonale antistoffer (mAbs) har blitt en viktig kilde for legemiddelutvikling og diagnostikk. Terapeutiske mAbs virker gjennom en rekke mekanismer, for eksempel blokkering av viktige signalveier. Hovedmålet i prosjektet har vært å utvikle en plattform for seleksjon, karakterisering og produksjon av mAbs. EffiBody-plattformen vil være mer pålitelig, raskere og mer kostnadseffektiv enn dagens metoder. Utvikling og produksjon av nye mAbs er dyrt og tidkrevende, dessuten er dagens metoder mindre pålitelige; bare halvparten av kommersielle brukte mAbs gjenkjenner korrekt mål. Den nye plattformen utviklet i dette prosjektet integrerer LC-MS / MS, NGS og bioinformatikkverktøy, i en plattform som representerer betydelig forbedring i forhold til dagens metode. Plattformen legge til rette for hurtig seleksjon av målspesifikke mAbs, fremfor dagens arbeidskrevende metoder for celleisolasjon og klondeteksjon. Ved å inkorporere bioinformatikkverktøy man kan redusere antall immuniseringseksperimenter og på den måten reduser ressurser bruken. Bioinformatikkverktøyer er basert data mining og tillater tolkning av komplekse genom- og proteomprofiler knyttet til seleksjon av antistoffer. Ved hjelp av Effibody-plattformen vil man effektivt, raskt og kostnadseffektivt kunne karakterisere, velge og produsere spesifikk mAb. De utviklede bioinfomatikk verktøyene vil bli tilbudt som en del av Plattformen, men i tillegg ha et betydelig potensial for fremtidige spin-out produkter. Konsortiet har så langt utviklet ulike potensielt terapeutiske mAbs for prostatakreft.

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.