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“Message in a Bottle” Cancer Therapy Shows Promise in Mice

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Researchers have used small membrane bubbles – which our cells use to communicate – to deliver targeted cancer treatments to tumors in mouse models, demonstrating reduced tumor growth and extended survival in one model.

The study is published in Nature Biomedical Engineering.

Innovations in targeted cancer therapies

Recent advances in anti-cancer therapies have led to the development of targeted antibody therapies. Antibodies seek out and bind to their target antigens with high affinity, allowing researchers to develop antibody-based drugs that target proteins, such as human epidermal receptor 2 (HER2), which drive the growth of breast cancer.

In a new study, researchers adapted this approach by using extracellular vesicles (EVs), which they liken to messages in a bottle. Cells use EVs to deliver signaling molecules to other nearby cells, which the researchers used to their advantage by loading EVs with chemotherapy drugs and attaching antibodies to their surface, enabling the targeted delivery of cancer treatments to tumor cells.

Showing promise in animal models

The research team developed EVs with antibodies targeting HER2 and programmed-death ligand 1 (PD-L1) to analyze their uptake by HER2-expressing cancer cells and melanoma cells, respectively. However, with this technology, the researchers suggest that the antibodies displayed on the EV surface could be adapted to target virtually any tissue of interest.

Experiments in vitro showed successful uptake of EVs by both melanoma and breast cancer cells. Studies in vivo using mice inoculated with melanoma or breast cancer cells showed that the EVs successfully localized to the tumors.

Next, the researchers investigated if EVs could be used for tumor-specific delivery of chemotherapy drugs. They loaded EVs with the chemotherapy drug doxorubicin and used them to target PD-L1 in the melanoma-bearing mice, discovering that the treatment reduced the animals’ tumor burden and extended their survival.

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The treatment could be even more flexible than this, according to the researchers. They have the potential to be adapted to display other antibody fragments, bispecific antibodies or antibody–drug conjugates, extending their use to other types of cancers.

“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,” said the study’s co-first author Oscar Wiklander, physician and researcher in the Karolinska Institute’s Department of Laboratory Medicine. “Therefore, the treatment has the potential to be used against other diseases and cancer types.”

The researchers hope this technique could be developed into a more specific and effective approach to eliminate tumor cells without affecting healthy tissue. Next, they plan to investigate if different combinations of antibodies and drugs could lead to further improvements in outcomes.

“Among other things, we want to investigate the possibility of delivering mRNA as an anticancer drug,” explained the study’s senior author Samir EL Andaloussi, a professor in the Department of Laboratory Medicine at the Karolinska Institute.

“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.”

Reference: Wiklander OPB, Mamand DR, Mohammad DK, et al. Antibody-displaying extracellular vesicles for targeted cancer therapy. Nat Biomed Eng. 2024:1-16. doi: 10.1038/s41551-024-01214-6

This article is a rework of a press release issued by the Karolinska Institute. Material has been edited for length and content.