Development and Clinical Translation Considerations for the Next Wave of Gene Modified Hematopoietic Stem and Progenitor Cells Therapies

ABSTRACT

Introduction

Consistent and reliable manufacture of gene-modified hematopoietic stem and progenitor cell (HPSC) therapies will be of the utmost importance as they become more mainstream and address larger populations. Robust development campaigns will be needed to ensure that these products will be delivered to patients with the highest quality standards.

Areas covered

Through publicly available manuscripts, press releases, and news articles – this review touches on aspects related to HSPC therapy, development, and manufacturing.

Expert opinion

Recent advances in genome modification technology coupled with the longstanding clinical success of HSPCs warrants great optimism for the next generation of engineered HSPC-based therapies. Treatments for some diseases that have thus far been intractable now appear within reach. Reproducible manufacturing will be of critical importance in delivering these therapies but will be challenging due to the need for bespoke materials and methods in combination with the lack of off-the-shelf solutions. Continued progress in the field will manifest in the form of industrialization which currently requires attention and resources directed toward the custom reagents, a focus on closed and automated processes, and safer and more precise genome modification technologies that will enable broader, faster, and safer access to these life-changing therapies.

KEYWORDS:

• Hematopoietic stem and progenitor cells
• development
• manufacturing
• process control
• stem cell transplant
• gene editing

Article highlights

• Overview of current state of advanced HSPC therapies.

• Perspective on applicable gene modification tools and technologies.

• Technology overview of various critical steps along the production process.

• Critical considerations for process and assay development.

• Important considerations during the manufacturing process to ensure a controlled, safe, and potent drug product.

Declaration of interest

M Li is an employee of Tome Biosciences. B Morse is an employee of Darkhorse Consulting group. S Kassim is an employee of Danaher Corporation. 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.