Antibody-displaying extracellular vesicles for targeted cancer therapy

Extracellular vesicles (EVs) are tiny particles naturally released by cells that serve as delivery vehicles for various biological signals and materials between tissues. Researchers are now leveraging the unique properties of EVs to create new, targeted cancer therapies.

The Power of EVs in Cancer Treatment

EVs have the potential to be powerful tools in medicine because they can naturally transport molecules to specific tissues. Scientists from the Karolinska Institutet have developed a way to enhance EVs with an antibody-binding component that specifically targets the fragment crystallizable (Fc) domain of antibodies. This modification transforms EVs into a flexible delivery system capable of targeting a wide range of tissues and cell types, making them particularly useful for cancer therapy.

Customizing EVs for Targeted Delivery

The engineered EVs, known as Fc-EVs, can be decorated with different types of immunoglobulin G (IgG) antibodies. Since IgG antibodies can be designed to target specific proteins on cancer cells, Fc-EVs can be directed to almost any tissue of interest. The researchers have optimized these EVs by testing various Fc-binding and EV-sorting components to ensure effective targeting and delivery.

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. 

Targeting Cancer Cells

In experiments, the optimized Fc-EVs successfully targeted cancer cells that express specific proteins such as the human epidermal receptor 2 (HER2) and the programmed-death ligand 1 (PD-L1). This precise targeting is crucial for delivering therapies directly to cancer cells while minimizing effects on healthy cells.

Enhanced Cancer Treatment in Animal Models

One of the most promising findings from this research was the use of Fc-EVs to treat melanoma tumors in mice. The EVs were decorated with an antibody targeting PD-L1 and loaded with the chemotherapy drug doxorubicin. When these engineered EVs were injected into the mice, they effectively reduced tumor size and extended the animals’ survival, demonstrating the potential for these EVs in cancer therapy.

Future Potential

The flexibility of Fc-EVs means they can be adapted to carry other therapeutic agents, including different types of antibodies, bispecific antibodies (which can bind to two different targets), and antibody-drug conjugates (which combine antibodies with potent drugs). This adaptability opens up a wide range of possibilities for treating various cancers and potentially other diseases.

The development of antibody-decorated EVs marks a significant advancement in targeted cancer therapy. By harnessing the natural delivery capabilities of EVs and combining them with the precision of antibody targeting, these researchers have created a powerful tool that could revolutionize how we treat cancer. This innovative approach holds promise for more effective and less toxic treatments, ultimately improving outcomes for patients.

Wiklander OPB, Mamand DR, Mohammad DK et al. (2024) Antibody-displaying extracellular vesicles for targeted cancer therapy. Nat Biomed Eng [Epub ahead of print]. [article]

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