Engineering of nano-sized membrane-vesicles for intracellular delivery of therapeutic antibodies

Purpose and goal

The project aimed at developing tailored biological carrier vehicles loaded with antibodies, with the ultimate goal of transferring antibodies into the cells cytoplasm to inhibit the mutated KRAS protein that is commonly found in most cancers. To this end, completely new techniques have been developed in an interdisciplinary collaboration involving the Royal Institute of Technology (engineering sciences), Karolinska Institute (pharmacological sciences), the Swedish Agricultural University (veterinary medicine) and the company Oblique Therapeutics AB.

Expected results and effects

We have developed and optimized a process to produce exosome-like nanovesicles from erythrocytes and load them with therapeutic drugs, including anti-KRAS antibodies produced by Oblique, showing promising results in colorectal cancer cells in vitro tests. The project led to the training of two doctoral students, one review article, three conference presentations, two additional articles in progress, and an innovative concept for the production of carrier vehicles from different membrane parts, which we hope to further develop for cell-targeting purposes in the future.

Planned approach and implementation

Projektet var indelat i fyra steg: (1) Produktion och laddning av bärarvehikler (2) Utveckling av tekniker för att optimera laddning (3) Undersökningar av bärarvehikelupptag till celler (4) Terapeutisk utvärdering. (1) SLU har framställt nya bärarvehikler från erythrocyter samt exosomer och utvecklat en process for deras laddning med Obliques antikroppar. KTH har utvecklat skräddasydda metoder för bäravehikelanalys och kvantifiering av laddningen. Karolinska institutet har utvärderat den inhibitoriska verkan av de ny framtagna antikroppar på odlade cancerceller.