Preclinical and clinical developments in enzyme-loaded red blood cells: an update

ABSTRACT

Introduction

We have previously described the preclinical developments in enzyme-loaded red blood cells to be used in the treatment of several rare diseases, as well as in chronic conditions.

Area covered

Since our previous publication we have seen further progress in the previously discussed approaches and, interestingly enough, in additional new studies that further strengthen the idea that red blood cell-based therapeutics may have unique advantages over conventional enzyme replacement therapies in terms of efficacy and safety. Here we highlight these investigations and compare, when possible, the reported results versus the current therapeutic approaches.

Expert opinion

The continuous increase in the number of new potential applications and the progress from the encapsulation of a single enzyme to the engineering of an entire metabolic pathway open the field to unexpected developments and confirm the role of red blood cells as cellular bioreactors that can be conveniently manipulated to acquire useful therapeutic metabolic abilities. Positioning of these new approaches versus newly approved drugs is essential for the successful transition of this technology from the preclinical to the clinical stage and hopefully to final approval.

KEYWORDS:

• Drug-loaded RBCs
• enzyme replacement therapy
• cancer therapy
• guanidinoacetate methyltransferase deficiency
• metabolic diseases
• RBC-derived extracellular vesicles
• therapeutic protein delivery
• toxic molecule removal

Article highlights

• A brief historical review of the use of red blood cells (RBCs) as a delivery strategy for therapeutic enzymes.

• The latest employments of enzyme-loaded RBCs for cancer treatment.

• A comprehensive and up-to-date overview of the exploitation of enzyme-loaded RBCs for the removal of toxic compounds, with additional annotations on treatment failures.

• Novel applications of RBCs engineered with an entire metabolic pathway for the treatment of rare diseases.

• A perspective on the future developments of RBC-derived Extracellular Vesicles (RBCEVs) as nanocarriers for drug delivery.

• A focused discussion of the technical challenges to be faced in making engineered RBCs a realistic and advantageous therapeutic option.

Declaration of interest

Mauro Magnani and Luigia Rossi hold shares in EryDel SpA, a company with interests in the technology of RBC-based drug delivery. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was partially supported by the European Union POR MARCHE FESR 2014/2020. Asse 1, OS 2, Azione 2.1-Intervento 2.1.1-Sostegno allo sviluppo di una piattaforma di ricerca collaborativa negli ambiti della specializzazione intelligente. Thematic Area: “Medicina personalizzata, farmaci e nuovi approcci terapeutici.”Project acronym: Marche BioBank www.marchebiobank.it.Marche BioBank research platform (POR MARCHE FESR 2014/2020).