Cell Therapies
THE FUTURE IS NOW
Joshua Ooi, Head, Treg Therapies Group
Cell therapies are a transformative new class of medicines that have been shown to cure cancer and, more recently, autoimmune diseases. These genetically engineered "living drugs", once thought to be science fiction, are accessible only to a small percentage of patients today. However, the field is rapidly evolving and may soon become a reality for many.
1. What are the most significant challenges the industry faces in bringing cell therapies to market?
Cost and disease target identification. The current cost associated with manufacturing cell therapies is very high. Cell therapies, albeit effective, are only approved for a small number of indications due to the lack of disease-specific targets.
2. What are the key factors driving the adoption of cell therapies in the Asia-Pacific region?
Therapeutic efficacy and evolution of closed-system manufacturing processes. It is clear from numerous clinical trials that cell therapies are powerful new medicines that can cure cancers as well as autoimmune diseases. The effectiveness of these new medicines has made the whole world pay attention particularly in the Asia-Pacific region, whereby revolutionary technological advancements like these can be applied to the millions and millions of patients that suffer from these diseases. Manufacturing is a key strength of the Asia-Pacific region, and there are now many companies that are investing into the development of cost-effective cell therapy processing. This is very exciting because these investments will ultimately lower the cost and increase accessibility.
3. What recent technological advancements are making cell therapies more viable and scalable?
Allogeneic therapy and large-scale facilities. Current cell therapies require cells from each individual patient as the starting material for developing the treatment. This boutique manufacturing process is a significant encumbrance. There have, however, been recent technological breakthroughs, including some which have shown efficacy in clinical trials, that show that cell therapies can be manufactured using an allogeneic source, i.e. cells donated from a healthy blood donor or from induced pluripotent stem cells. This significant advancement means that cell therapies could soon become an off-the-shelf therapy. Current standard manufacturing processes are also very small scale; very expensive highly-specialized machines are literally limited to producing one treatment dose for one patient over a two-to-three week period. The development of large scale production facilities will make cell therapies both commercially viable and scalable.
4. How do you see AI, automation, or digital platforms playing a role in the development and administration of cell therapies?
I foresee artificial intelligence (AI) playing a significant role in the identification of novel disease targets as well as in the design of receptors that will specifically bind to those targets. Currently, for example, cell therapies work really well for blood cancers because there is a specific target on the cancerous blood cell. However, this treatment does not work for other cancers because of the lack of targets. AI will enable the analyses of billions and billions of DNA sequences to identify which targets are unique to the cancer and will be expressed on the surface of the cancer cell. Then, AI will also accelerate the design of complementary receptor sequences that will bind specifically to the unique cancer target.
Automation is another key piece of the cell therapy accessibility puzzle. Current closed-system manufacturing processes are highly labour intensive, thus making the whole process expensive and vulnerable to operator error. As robotic technology advances, more advanced systems are being built, whereby the manufacturing process is streamlined to the point where it is almost fully automated. Thus, costs are reduced and manufacturing issues are minimized.
5. What unique challenges arise in designing and conducting clinical trials for cell therapies compared to other treatments?
Large scale clinical trial data and control groups. Due to the high cost of cell therapies and the invasive nature of producing the treatment (i.e. leukapheresis, lymphodepletion, ICU stay, etc.), it is currently impossible to perform large scale Phase III clinical trials as expected of other forms of therapeutics e.g., small molecule inhibitors or monoclonal antibodies. Furthermore, it is unethical to make a patient undergo the process of collecting cells without giving the manufactured cells back to the patient. Thus, there are no placebo treated groups in the clinical trials. Therefore, trial design is significantly different and needs to be tailored specifically to the disease cohort.
6. Cell therapies are often expensive. How is the industry working to make these treatments more accessible?
The industry is investing heavily in the development of off-the-shelf allogeneic therapies as well as fully automated large-scale manufacturing processes. Recent innovations in both genetic engineering and robotics now mean cells can be manufactured at a much lower cost. For example, mRNA technology which was rolled out worldwide during the COVID-19 pandemic, can be repurposed to manufacture cell therapies at a fraction of the current cost which utilizes a much more expensive lentivirus technology. There is also significant competition from various closed-system manufacturers which has accelerated innovation in the space and led to a significant reduction in the price of machinery. As more and more Asia-Pacific countries realize the potential of cell therapies, government interest and likely subsidies will further drive down the cost of manufacturing cell therapies.
7. How can stakeholders work with payers to ensure reimbursement models that support the adoption of cell therapies?
To support the adoption of cell therapies, stakeholders (i.e. the pharmaceutical industry) can educate the payers (i.e. health insurance funds, government health agencies and private patients) of the long-term benefits of cell therapies. For example, although cell therapies may be a significant upfront cost relative to conventional treatments, a single-dose of a cell therapy can effectively cure disease with no need for repeat treatments. In the case of autoimmune diseases like lupus, patients who have received cell therapies can live their lives steroid-free.
8. Where do you see the field of cell therapies heading in the next decade?
I see rapid development and adoption of novel cell therapies. Based on the successes of cell therapies in the field of oncology, and more recently autoimmunity, there is now massive investment from both government funding agencies and the biopharmaceutical industry to further develop the applicability and accessibility of cell therapies. This means that cell therapies will be able to treat many more diseases and the costs associated with these therapies will be affordable to many more patients.
9. What role do collaborations between biotech companies, academia, and governments play in advancing cell therapies?
Collaboration between biotech companies, academia and governments are key to unlocking the full benefits of cell therapies. Academia, through government funded research, is where fundamental breakthrough discoveries happen. These discoveries in basic biology help us to understand new disease pathways, and in the context of cell therapies, lead to the discovery of new targets for treatment. Then, through collaboration with biotech companies, investment in the validation of these novel targets will lead to treatment candidates for clinical trial testing. Furthermore, biotech and pharmaceutical companies have the machinery and distribution capabilities to deliver new treatments to patients.
10. What advice would you give to companies or researchers entering the cell therapy space today?
Differentiate. Cell therapies have really only just begun and there are many avenues that a company or researcher can carve a niche for themselves. For example, identify a new target, or a new receptor for that target or innovate the cell processing machinery. These are definitely exciting times in the cell therapy space.
Author Bio
A/Prof. Ooi is Head of the regulatory T cell therapies laboratory at Monash University, an Australian NHMRC Leadership Fellow and co-founder of Resseptor Therapeutics. A/Prof. Ooi is a leader in the field of autoimmune diseases, and has received many prestigious prizes for his work including the international Mosaic of Autoimmunity Award and the Victoria Prize for Science and Innovation.
