Surface-Engineered Natural Killer Cell-Derived Small Extracellular Vesicles Induce Potent Anti-Tumour Effects in Lung...

Area of Science:

• Immunotherapy
• Extracellular Vesicles
• Oncology

Background:

• Natural killer cell small extracellular vesicles (NK-sEVs) offer cell-free therapy with inherent anti-tumour properties.
• Genetic engineering presents an opportunity to enhance NK-sEVs for targeted cancer treatment.

Purpose of the Study:

• To engineer NK-sEVs to express interleukin 15 (IL15) and cetuximab for improved anti-tumour immunotherapy.
• To evaluate the tumour-targeting capabilities and anti-cancer efficacy of these modified NK-sEVs (eEVs).

Main Methods:

• Lentivirus-based modification was used to create IL15- and cetuximab-tethered NK-sEVs (eEVs).
• In vitro binding assays confirmed cetuximab-mediated targeting of EGFR+ cancer cells.
• In vivo studies utilized a lung cancer mouse model to assess eEVs' anti-tumour efficacy.

Main Results:

• Engineered eEVs selectively bound to EGFR+ cancer cells.
• eEVs demonstrated significantly enhanced cytotoxicity compared to control NK-sEVs, inducing cancer cell death and promoting NK cell killing.
• In vivo, eEVs accumulated in tumours and suppressed tumour growth, both alone and in combination with anti-PD-1 therapy.

Conclusions:

• Genetically engineered NK-sEVs (eEVs) expressing IL15 and cetuximab exhibit potent anti-tumour activity and enhanced tumour-targeting capabilities.
• eEVs show significant potential as a novel immunotherapeutic strategy for cancer treatment, particularly in combination therapies.