Scalable Biomanufacturing Workflow to Produce and Isolate Natural Killer Cell-Derived Extracellular Vesicle-Based Cancer Biotherapeutics

作者： Frederic St-Denis-Bissonnette*1,2, Melanie Kirkby*1,2, Lisheng Wang2,3,4, Jessie R. Lavoie1,2 1Biologic and Radiopharmaceutical Drugs Directorate, 2Department of Biochemistry, Microbiology and Immunology Institute,University of Ottawa, 3Centre for Infection, Immunity and Inflammation Institute,University of Ottawa, 4Regenerative Medicine Program,Ottawa Hospital Research Institute

简介：

Overview

This study presents a scalable biomanufacturing workflow for the continuous production and isolation of high-purity natural killer cell-derived extracellular vesicles (NK-EVs). The methodology ensures that the vesicles meet quality standards for therapeutic applications in cancer treatment.

Key Study Components

Area of Science

• Immunology
• Cancer Biology
• Biomanufacturing

Background

• Natural killer cells are immune cells with the ability to kill cancer cells.
• Extracellular vesicles (EVs) derived from these cells have therapeutic potential.
• Current methods for isolating NK-EVs often lack scalability and purity.
• This study addresses these challenges with a novel biomanufacturing approach.

Purpose of Study

• To develop a closed-loop biomanufacturing workflow for NK-EVs.
• To ensure high purity and scalability of NK-EV production.
• To facilitate further research into the therapeutic applications of NK-EVs.

Methods Used

• Isolation of NK-EVs using size exclusion chromatography with bimodal resin.
• In-process control testing throughout the biomanufacturing workflow.
• Sterilization and concentration of isolated NK-EVs.
• Nanoparticle tracking analysis to characterize NK-EV size and concentration.

Main Results

• The workflow produced NK-EVs with an average size of 76.30 to 174.30 nanometers.
• Average concentration of NK-EVs was 1.39 x 10^12 EVs per milliliter.
• High purity was achieved, making the technique suitable for therapeutic applications.
• Results support the potential of NK-EVs in treating solid tumors.

Conclusions

• The developed biomanufacturing workflow is scalable and efficient.
• NK-EVs show promise as a biotherapeutic for cancer treatment.
• Further research is needed to explore their therapeutic mechanisms.

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