Body’s ‘message in a bottle’ delivers targeted cancer treatment

Photo: Getty Images

Extracellular vesicles are small bubbles that cells can send to each other to exchange information. Image: Getty Images

Researchers at Karolinska Institutet have succeeded in delivering targeted cancer treatment via small membrane bubbles that our cells use to communicate. A new study published in Nature Biomedical Engineering shows that the treatment reduces tumour growth and improves survival in mice.

When our cells communicate, they send out small membrane bubbles known as extracellular vesicles which contain various signalling molecules. Interest in these tiny bubbles, sometimes referred to as the body’s ‘message in a bottle’, has increased in recent years as they could be used to deliver medicines.

Antibodies seek out tumours

Researchers at Karolinska Institutet have now created a targeted cancer treatment by loading these bubbles with a chemotherapeutic drug and attaching antibodies against tumours to their surface. In addition to targeting tumour cells, the antibodies act as a form of immunotherapy, resulting in an enhanced therapeutic effect. The treatment reduced tumour growth and improved survival when given as an injection to mice with breast cancer or melanoma.

“By attaching different antibodies to extracellular vesicles, we can target them to virtually any tissue and we can load them with other types of drugs as well,” says Oscar Wiklander, physician and researcher at the Department of Laboratory Medicine, Karolinska Institutet, and joint first author with Doste Mamand, researcher at the same department. “Therefore, the treatment has the potential to be used against other diseases and cancer types.”

Engineering cells to produce EVs decorated with
an antibody-binding moiety specific for the Fc domain

Fig. 1

The producer cells are transduced with a construct to produce EVs that display an Fc-binding domain (Fc-EVs) that can be decorated with different types of antibody (mAb), loaded with therapeutic cargo (drug) and targeted to virtually any tissue of interest, such as cancer cells.

More effective and fewer side effects

The hope is that the new treatment will be more specific and effective in eliminating tumour cells without affecting healthy tissue, compared to current treatment strategies. The researchers plan to investigate whether different combinations of antibodies and drugs can further improve treatment.

“Among other things, we want to investigate the possibility of delivering mRNA as an anticancer drug,” says the study’s last author Samir EL Andaloussi, Professor at the Department of Laboratory Medicine, Karolinska Institutet. “Ultimately, we hope this can lead to a new treatment platform that can improve treatment efficacy and reduce side effects in difficult-to-treat diseases, especially cancer.”

The research was mainly funded by the Swedish Cancer Society, the Swedish Research Council, the European Research Council (ERC) and CIMED. Several of the authors have a financial interest in Evox Therapeutics.

Wiklander OPB, Mamand DR, Mohammad DK, Zheng W, Jawad Wiklander R, Sych T, Zickler AM, Liang X, Sharma H, Lavado A, Bost J, Roudi S, Corso G, Lennaárd AJ, Abedi-Valugerdi M, Mäger I, Alici E, Sezgin E, Nordin JZ, Gupta D, Görgens A, El Andaloussi S. (2024) Antibody-displaying extracellular vesicles for targeted cancer therapy. Nat Biomed Eng [Epub ahead of print]. [article]

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