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Scalable Biomanufacturing Workflow to Produce and Isolate Natural Killer Cell-Derived Extracellular Vesicle-Based Cancer Biotherapeutics
Published on: August 16, 2024
NK cells-derived extracellular vesicles potency in the B cell lymphoma biotherapy
Serena Cecchetti1, Cristina Federici2, Rossella Canese3
1Core Facilities, Confocal Microscopy Unit, Istituto Superiore di Sanità, Rome, Italy.
Introduction:
Extracellular vesicles of Natural Killer cells (NKEV) exert an antitumor effect towards hematopoietic and solid tumors and have an immune modulating effect, suggesting a promising role in immune and biotherapy. In this study, a continuation of our former works, we demonstrated a network by mass spectrometry analysis between NKEV protein cargo and antitumor effects. Human healthy NKEV, both exosomes and microvesicles, have a significant and direct cytotoxic effect against human B cell lymphoma in in vitro and in vivo conditions.
Methods:
We isolated extracellular vesicles from in vitro amplified healthy human NK cells and their treatment efficacy was monitored by cytometry analyses, in vivo MRI/MRS measurements, ex vivo MRS analyses and immunohistochemistry.
Results:
We observed a remarkable NKEV cytotoxic effect, mainly by apoptosis, on B cell lymphoma in vitro when exosomes and microvesicles were administered simultaneously. In vivo results showed metabolic alterations in SCID mice xenografts after NKEV treatment, associated with a significant reduction of tumor growth (64%). In the in vivo 1H MR spectra we found a significant increase in the tumor lipid/lactate and in taurine signals, both considered as apotosis markers. Ex vivo lymphoma metabolomics revealed a significant increase in fatty acid (FA) pool and decrease in unsaturated and mono-unsaturated FA in treated groups, as compared to control one, thus suggesting an alteration of tumor homeostasis. Immunohistochemistry analyses confirmed the reduction of B-cell lymphoma proliferation rate, as well as the induction of apoptosis following the NKEV treatment.
Conclusions:
This study underscore the importance of NKEV as a novel biological acellular tool for B-cell lymphoma treatment, probably having a greater effect on combined treatment regimens. These nanovesicles have an extraordinary potential in innovative cancer immunotherapy, representing a safe and efficient tool naturally circulating in healthy individuals and ready to maintain the immune homeostasis, and therefore a good organism healthy state.
Insights
Natural Killer cell extracellular vesicles (NKEV) show direct cytotoxic effects against B cell lymphoma. This study highlights NKEV as a promising acellular tool for innovative cancer immunotherapy and potential treatment regimens.
Area of Science:
- Immunology
- Biotherapy
- Cancer Research
Background:
- Natural Killer cell extracellular vesicles (NKEV) possess antitumor and immune-modulating properties.
- Previous research indicated NKEV's potential in treating various cancers.
- This study further investigates the therapeutic network and efficacy of NKEV.
Purpose of the Study:
- To demonstrate the network between NKEV protein cargo and antitumor effects using mass spectrometry.
- To evaluate the direct cytotoxic effect of human healthy NKEV against B cell lymphoma.
- To assess the in vitro and in vivo efficacy of NKEV in B cell lymphoma models.
Main Methods:
- Isolation of extracellular vesicles from in vitro amplified human NK cells.
- Monitoring treatment efficacy using cytometry, in vivo MRI/MRS, ex vivo MRS, and immunohistochemistry.
- Mass spectrometry analysis of NKEV protein cargo.
Main Results:
- NKEV exhibited significant in vitro and in vivo cytotoxic effects on B cell lymphoma, primarily through apoptosis.
- In vivo treatment led to a 64% reduction in tumor growth with observed metabolic alterations.
- Increased apoptosis markers (lipid/lactate, taurine) and altered fatty acid profiles were detected in treated tumors.
Conclusions:
- NKEV represents a novel biological acellular tool for B-cell lymphoma treatment.
- Combined NKEV treatment regimens may enhance therapeutic effects.
- NKEV holds significant potential for innovative cancer immunotherapy and maintaining immune homeostasis.
