Editor's note: In this installment of Expert Opinion, Suzanne Snellenberg, PhD, Director of Genome Engineering at Cellistic, shines a spotlight on the importance of gene editing in successful cell therapy and on scientific milestones reached by the Cellistic team in its first year.
Looking at the rapidly evolving world of genome editing and how it is facilitating ground-breaking discoveries in multiple therapeutic areas. Can you tell us more about its key relevance for developing successful cell therapies.
Gene editing is foundational to so many aspects of cell therapy that the field as we know it would hardly exist without genetic engineering capabilities. For example, gene editing allows for targeted integration of specific genes, like chimeric antigen receptors (CARs), thereby enhancing the ability of T-cells to target cancer cells in immunotherapy. This type of targeted integration – which is virtually impossible without gene editing – has become a routine process at Cellistic to improve the functionality of immune cells and their ability to recognize and eliminate cancer cells. In addition, our gene editing approach will allow multiple modifications to be combined in an allogeneic cell therapy strategy.
To summarize, gene editing makes off-the-shelf cell therapies feasible by modifying cells to evade immune attack, improve overall compatibility, and prolong the survival of transplanted cells and the need for immunosuppressive drugs. So where would cell therapy be without the power of gene editing?
Why is it even more important in terms of developing allogeneic cell therapy strategies for immune cells?
Gene editing is crucial in ensuring the safety of allogeneic cell therapies by offering precise control over the modification of donor cell genes. This targeted approach enables the elimination or alteration of genes associated with graft-versus-host disease (GVHD), an immune-mediated disorder that can occur after allogeneic stem cell transplantation. Through gene editing techniques, the risk of GVHD and other adverse immune reactions can be significantly reduced, leading to enhanced safety and tolerability of allogeneic cell therapies. This targeted modification also expands the compatibility of the therapies, minimizing the risk of immune rejection among a broader range of recipients, and facilitating a more scalable and accessible therapeutic approach. In addition, gene editing plays a pivotal role in the development of standardized and scalable manufacturing processes for allogeneic cell therapies. This scalability enhances production efficiency, lowers costs, and increases the availability of allogeneic cell therapies for a larger patient population.
Cellistic launched only 13 months ago. It would be unusual if you’d reached any breakthroughs in gene science. But have you? If not, what one or two achievements make you proudest or demonstrate that your young team has a bright scientific future?
Generating cells with multiple genetic alterations using the CRISPR technology poses challenges, particularly in sensitive iPSCs. Delivering CRISPR components efficiently poses a challenge in iPSCs due to their lower transfection and editing efficiencies compared to other cell types. Simultaneously, it’s crucial to ensure that the pluripotent state of iPSCs is maintained throughout the gene editing process. Isolating individual cells and deriving clonal cell populations with the desired genetic modifications is another significant hurdle in genome editing procedures for iPSCs.
At Cellistic, we’ve solved this challenge by developing a streamlined pipeline specifically for producing gene-edited iPSCs. Our approach has demonstrated remarkable success, with editing efficiencies reaching up to 90 percent and over 50 percent recovery rates from single iPSCs. In short, we’re on a good trajectory already, and we’ve got a bright scientific future ahead as we drive toward bringing Cellistic’s full capabilities to market.
Can you explain Cellistic’s approach on cell line development: what makes it unique, and how does it benefit clients?
Cellistic leverages more than ten years’ worth of Ncardia's expertise in designing and refining manufacturing platforms for iPSC-based cells. These platforms enable large-scale production of high-quality products. Our cell line development platform empowers us to swiftly progress from initial concepts to edited iPSCs, utilizing purpose-built facilities. We leverage precise and well-established reprogramming, gene editing, and cell banking techniques, saving our customers months of valuable time. Our team has also implemented dedicated quality systems that incorporate stringent process controls and robust analytical testing strategies. These measures ensure that our outcomes consistently meet high-quality standards while maximizing efficiency. With our comprehensive capabilities and commitment to quality, we believe Cellistic is poised to drive advancements in the field of iPSC-based cell manufacturing.
To date, only a handful of therapies based on gene editing have been approved in Europe and the US. There is talk about reaching a “critical mass phase” when enough research has been conducted that drugs begin receiving approvals regularly. How long do we have to wait to reach that phase?
The timeline for reaching a "critical mass phase" of regular approvals for gene editing therapies is difficult to predict due to various factors like research pace, clinical trial outcomes, regulation, and ethics. This timeline is even more difficult to predict for cell therapies created through gene editing. Cell therapies have unique considerations such as manufacturing, quality control, and cell behavior in the body, making their approval process distinct from traditional drugs. While a specific timeframe is challenging to provide due to scientific advancements' dynamic nature, we expect an increasing number of gene-edited cell therapies to receive regulatory approvals in the coming years.
Given the costs associated with gene editing, what types of cell therapy projects are suited to this approach? Are some projects – or budgets – simply too small or narrow to absorb these costs?
As gene editing costs can be significant, it is particularly suitable in cell therapy projects for conditions where precise genetic modifications are essential for therapeutic effectiveness. CAR-based cell therapies serve as an excellent example of this. When deciding to pursue gene editing in a cell therapy project, considerations should include the disease's severity, potential therapeutic advantages, available resources, and feasibility within budgetary limitations.
iPSCs have the potential to absorb costs in allogeneic cell therapy production. By using a consistent source of iPSCs, manufacturing costs associated with cell line establishment and cell variability can be reduced. In addition, iPSCs have the ability to proliferate indefinitely, enabling the production of a greater number of doses from a single iPSC line.
Cellistic has invested a lot of time, energy and resources in cell line development. What has been learned from those efforts also helps reduce lead times and costs. Additionally, we believe that collaborations, partnerships, and advancements in gene editing technologies have the potential to reduce costs and enhance accessibility of gene editing for a broader range of cell therapy projects in the future.
Contact us if you want to learn more about how Dr. Suzanne Snellenberg and the Cellistic team can help you advance your therapy.