Cell Therapies have completely transformed healthcare by harnessing the power of live cells to both treat and prevent diseases. During a recent Q&A session with Behzad Mahdavi, Executive Chairman of the Board of Directors at OpenCell Technologies, Inc., we explored the fundamental principles and essential methodologies underpinning this groundbreaking field. Our discussion extended to elucidating the distinctive mechanisms behind various types of cell therapy treatments available in the market today. Furthermore, we delved into the ongoing clinical trials and their prospective impact on healthcare, shedding light on the promising future of this innovative medical frontier. Meanwhile, Behzad highlighted the contribution of OpenCell Technologies to this ever evolving sector.
#LBS: Cell therapy has unquestionably become a game-changer in the healthcare sector. To delve deeper into this innovative field, could you provide a more detailed explanation of the core principles and key methodologies involved in cell therapy and how these advancements are revolutionising healthcare?
Behzad Mahdavi: Cell therapy involves the use of living cells to treat or prevent diseases. The core principles revolve around harnessing the therapeutic potential of cells, typically stem cells (or its derivative like Exosomes) or immune cells, to replace, repair, or enhance biological functions. Key methodologies include the isolation and culture of cells, their manipulation or modification in the laboratory leveraging transfection or transduction technologies coupled with gene-editing technologies, and subsequent infusion or transplantation into the patient.
In the case of stem cell therapy, pluripotent or multipotent stem cells can differentiate into various cell types, promoting tissue regeneration. Immune cell therapy, such as CAR-T cell therapy, involves engineering T cells to upgrade and rectify our immune system so the T cells, the soldiers of our body, can target and destroy cancer cells in a curative way. These advancements are revolutionising healthcare by offering, in some cases, curative therapies with higher precision and personalization. They represent in most of the cases more targeted and personalised treatment approaches, with the potential to address previously untreatable conditions and reduce the reliance on traditional drugs or surgeries.
At OpenCell Technologies, we are working to lower the barrier to entry for these life-saving cell therapies through improving the way molecules used to genetically modify cells are delivered to cells. By streamlining the process to go from benchtop experimentation to delivery of cells or cell-derivatives to patients, our goal is to bring these revolutionary cell therapies to market quicker, less costly and in a scalable way to provide greater healthcare equity.
#LBS: The landscape of cell therapeutic treatments is constantly evolving. Could you elaborate on the specific types of cell therapy treatments available in the market, their unique mechanisms, and any notable breakthroughs or limitations associated with them?
Behzad Mahdavi: The landscape of cell therapeutic treatments is indeed dynamic, encompassing various types of cell therapies with unique mechanisms. Three primary groups of cell therapies highlight this diversity: those operating based on a secretory mechanism, those involved in tissue creation, and those designed with specific functions.
In the first group, mesenchymal stem cell (MSC) therapy exemplifies a secretory mechanism. MSCs release bioactive factors, including exosomes, as the active therapeutic ingredient. These exosomes play a crucial role in promoting tissue repair and modulating the immune response, making MSC valuable in treating conditions such as autoimmune diseases or tissue injuries. However, these secretory-based therapies have a temporary effect, and achieving a balanced business case and application, considering cost and benefits, poses economic challenges. Large-scale manufacturing is another obstacle in reducing costs to achieve this balance. As emphasised in my newly published book, "Mastering Commercial Innovation," success requires the right balance between Technology, Market needs, and Finance. In the case of MSC, equilibrium is not fully achieved, but exosomes might hold a more promising future.
The second group includes therapies focused on creating tissues, with induced pluripotent stem cell (iPSC) therapy being a notable example. iPSCs are generated by reprogramming adult cells to exhibit embryonic stem cell-like properties. They can then be differentiated into various cell types to repair or replace damaged tissues, offering potential treatments for degenerative diseases. However, this group also faces challenges related to scalability and cost and is still at its very early stage of development.
The third group encompasses therapies designed with specific functions, such as immune cell therapy like CAR-T cell therapy. This approach involves modifying a patient's T cells to express chimeric antigen receptors (CARs), enabling them to recognize and target specific cancer cells. This personalised immunotherapy has shown remarkable success in treating certain blood cancers. This group holds very high promise and needs biologic optimization for manufacturability to decrease costs and increase scale, as described in a 2015 publication (https://themedicinemaker.com/manufacture/the-hype-hope-and-reality-of-personalization).
In general, Cell and Gene Therapy has limitations, which may be economic (COGS), therapeutic-related outcomes, manufacturing scalability-related, or a combination of all factors. Most therapies currently lack scalability and reasonable cost. While these powerful therapies have not been fully optimised for manufacturing, artisanal manufacturing processes are currently involved. It is time to shift towards manufacturing optimised products using biologically optimised therapies for manufacturing and use scalable platforms from the early stages of development, as it is very risky to switch during the development process. The diversity of methods used in cell therapies has prevented turnkey solutions from being created and have resulted in a fractured manufacturing process.
#LBS: Given your dedication to fostering the growth and maturity of the cell therapy industry, could you delve into some of your most influential projects and their specific objectives? What potential outcomes and long-term impacts do you anticipate for both the industry and patients?
Behzad Mahdavi: Throughout my career in Cell and Gene Therapy (CGT), I've adhered to a threefold approach, emphasising Quality, Quantity, and Cost as the pillars of successful therapy. Quality encapsulates the crucial elements of safety and efficacy, while Quantity focuses on developing scalable platforms capable of meeting market demand. Cost is a multifaceted consideration, addressing both accessibility for patients/payers and the need for a robust return on investment to compensate for inherent risks.
In past endeavours, I've spearheaded disruptive and innovative technologies to elevate the success of CGT. Notable examples include introducing an autonomous patient-scale bioreactor for Autologous Cell Therapy, as highlighted in: https://themedicinemaker.com/manufacture/the-hype-hope-and-reality-of-personalization. Additionally, I led the charge in establishing industrial manufacturing processes for exosomes, concentrating on effective characterization to enhance scalability and reduce costs.
Presently, my focus with OpenCell Technologies revolves around pioneering scalable methods for non-viral transfection. Recognizing the future potential of non-viral delivery methods, particularly in gene editing, our team at OpenCell has developed a groundbreaking continuous, non-viral, and highly scalable transfection method—especially tailored for large cargos. This innovative approach opens new horizons in the field, promising advancements in safety, scalability, and cost-effectiveness for cell therapies. Through automation and tunable control of molecule delivery, OpenCell is developing platforms to address the current limitations in the cell and gene therapy process. By standardising the method of delivery to cells, OpenCell is looking to unlock the potential for cell therapies to reach to market faster, reduce the cost of treatment for patients, and create new avenues of treatments.
My dedication to introducing disruptive and transformative technologies underscores a commitment to advancing the CGT industry and improving patient outcomes. By continually addressing the evolving needs and challenges within the field, my work strives to contribute to the ongoing progress and success of cell and gene therapies and broader Pharma in the area of Oral delivery with the TIM Company which can be also a door opener for Orla exosomes delivery.
#LBS: Could you provide a more comprehensive overview of the current clinical trials for cell therapy, including the conditions they aim to address and the potential implications for the future of healthcare if these trials yield positive results?
Behzad Mahdavi: There's a notable recognition of the transformative and one-time-use capabilities observed in both cell therapies and gene therapies, emphasising their curative potential. In my perspective, it's time to shift the focus towards not only the therapeutic efficacy and safety but also the optimization of products both biologically and in terms of processes, specifically geared for scalable manufacturing and cost reduction. The industry has been predominantly concentrated on achieving efficacy and safety milestones, and it's now opportune to address the equally critical criteria of scalability and cost-effectiveness.
This shift signifies a departure from manufacturing sub-optimally designed products towards the production of truly optimal ones, ensuring enhanced efficiency and manufacturability. By striking a balance between therapeutic effectiveness and the practical aspects of large-scale manufacturing, we can usher in a new era where these groundbreaking therapies become more accessible and sustainable. The need for this shift is exemplified in the CAR-T field in that existing CAR-T therapies are autologous, meaning that the T-cells are derived from a single patient, and following genetic modification, the cells are reinfused into the same patient. This therapeutic modality is inherently costly and unscalable. The future is in allogeneic CAR-T therapy whereby many T-cells from a number of donors are harvested, modified and manufactured as an off-the shelf therapy for any appropriate patient. Manufacturing allogeneic CAR-T therapies, however, will require the scalability of a delivery technology such as OpenCell’s poration technology.
Two areas that hold significant potential for future breakthroughs are, firstly, gene editing delivery, as discussed earlier. This avenue presents an exciting frontier where precise modifications can be efficiently delivered, unlocking possibilities for treating genetic disorders with unprecedented accuracy.
Secondly, the ongoing exosome therapy trials represent a promising field of exploration. These clinical trials are actively investigating the therapeutic properties of exosomes derived from cells, aiming to harness their potential for tissue repair, immune modulation, and the treatment of diverse diseases. Success in these trials could introduce a paradigm shift in therapeutic interventions, offering alternatives that are not only effective but also potentially more accessible and targeted. The potential of drug for oral delivery is another potential avenue for Extra Cellular Vesicles.
In summary, while acknowledging the remarkable curative abilities of cell and gene therapies, it's imperative to direct our attention towards optimising products for scalability and cost reduction. Simultaneously, the fields of gene editing delivery and exosome therapy trials hold tremendous promise, offering avenues for precise genetic interventions and innovative therapeutic approaches, respectively, that could redefine the landscape of healthcare.
#LBS: The London Biotechnology Show strives to showcase groundbreaking developments in the biotech field to a global audience. What is your perspective on the significance of such events for the industry and its advancement?
Behzad Mahdavi: The London Biotechnology Show serves as a powerhouse for global biotech advancements. This event is a dynamic hub where industry leaders converge to unveil groundbreaking developments, fostering collaboration, and accelerating innovation. It's a crucial platform for showcasing cutting-edge technologies, sparking collaborations, and propelling the entire biotech industry forward on a global scale. The exposure and connections made at such shows are instrumental in shaping the future trajectory of biotechnology, making these events indispensable for industry progress.
