Autologous and Allogeneic Cell Therapies: Benefits, Challenges, and Future Prospects

Cell and gene therapies (CGT) are at the frontline of clinical research and offer the potential to transform treatment for serious medical conditions. There are two types of cell therapies in development – autologous and allogeneic. Each provides distinct clinical and production advantages and challenges, and therapeutic capabilities. In this blog, we explore both autologous and allogeneic approaches, the solutions needed to optimize the development processes for commercial viability, and the future landscape of cell therapies in the rare disease space.

Understanding Autologous Therapies

Autologous therapies are proven to have the potential to significantly improve clinical outcomes in patients or cure rare diseases. In autologous therapies, the patient donates their own cells as starting material. These cells are then cultured, expanded, and modified ex vivo or outside of the body, and reintroduced back into the patient as a therapeutic intervention. Autologous products are specially tailored to the patient and cannot be administered to other individuals. Since an autologous therapy is derived from the patient, there is also minimal risk of adverse autoimmune complications post-transplant such as graft versus host disease (GvHD).

Challenges of autologous therapies 

Despite the success of autologous therapies, this method poses several challenges in clinical development, production, and potential therapeutic capabilities. These challenges include:

• Clinical outcomes – Reliance on sick patients for starting material poses a key challenge. Not all patients are considered viable candidates for autologous therapy due to the lack of adequate starting material. Unqualified patients may experience delayed treatment or never receive treatment at all. For qualified patients, prior treatment and the disease itself can still impact the quality of the starting material and affect the quality of the final product. Autologous methods also present a challenging timeline. The entire process from pre-treatment preparation to cell collection to drug production can take up to 12 weeks to return to individuals. This is not feasible for end-of-life patients who are battling a rare disease with aggressive progression. 

• Complex manufacturing – Developing personalized medicines is inherently prone to high operating costs and product variability. Since autologous therapies are unique to each patient, there is high variability at the start of the manufacturing process, making it difficult to achieve reproducible results across multiple products. This calls into question the commercial viability of cell and gene therapies outside of the rare disease space.
  
  
• High cost, low yield approach- Realistically, autologous products can only treat a handful of patients each year post-market. As a result, autologous therapies are extremely expensive to develop and costly for patients which leads to low engagement with payers or insurance companies and national health care providers.
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• Patient inaccessibility – There are only a few centers globally that offer autologous therapies. Not all hospitals or medical facilities have the necessary staff, equipment, and capabilities to administer advanced cell therapies. Even if payers are willing to pay for the therapy itself, patients and caregivers often have to self-fund their own travel and accommodation. They must also consider the pre- and post-treatment protocols required for autologous therapy. In combination, patients are spending quite a lot of time out of work or school just to receive these types of treatments. 

Although autologous therapies are here to stay, this high cost, low yield approach is not sustainable long-term. Autologous therapies are therefore a non-viable option for manufacturers and patients. 

Understanding Allogeneic Therapies 

Rather than using the patient’s own cells and starting material, allogeneic therapies are derived from cell sources from healthy donors, stem cell sources or cell banks. These healthy sources provide a reliable number of functional cells. The starting material goes through various stages of differentiation, expansion, modification, and activations before the final product is released for administration to the actual patient. 

Since allogeneic therapies are derived from healthy sources, the starting material offers a greater quantity of functional cells. Allogeneic methods also allow for the development of many treatments from a single, reliable source. One batch has the potential to yield hundreds or even thousands of doses for a larger patient population. The cost of an allogeneic therapy can therefore be significantly lower per dose than compared to autologous therapies. In theory, you can send an off the shelf, final product to any patient at any center in the world, improving patient accessibility and engagement globally. 

Challenges of allogeneic therapies 

Although allogeneic methods can potentially circumvent production obstacles, there are several challenges that must be resolved before its potential is fully realized.

• Expensive starting material – Due to the lack of availability of clinical grade lines, starting material for allogeneic therapies is costly. As a result, we are seeing some companies investing in the development of cell libraries and cell banks before investigating allogeneic therapies in preclinical and clinical trials.
  
  
• High safety risk - Since allogeneic products are derived from donors, there may be residual, non-modified foreign cells in the final product that may trigger an immune reaction in the receiving patient. To ensure patient safety, a final product must be as pure as possible. Unfortunately, there is no consensus on what assay to use to confirm whether the percentage of non-modified cells remaining is within safe limits and what those limits are. Several organizations within Europe and the U.S. are currently working to validate assays to be approved by regulatory agencies.
  
  
• Complex manufacturing – The field needs to develop higher throughput technology to remedy the complexity of the current scale-out manufacturing model.

Allogeneic cell therapies have the potential to disrupt the industry and rare disease space. However, it is critical to develop solutions to relieve manufacturing obstacles, high costs, and concerns about immunological risk and long-term safety.

The Future Landscape of Cell and Gene Therapies

The industry is seeing increasing competition for rare disease patients in CGT studies, a complex and continuously evolving regulatory environment, clinical trial capacity constraints, and manufacturing limitations. At present, the availability of fully characterized, consistent, and validated starting materials has posed significant limitations in this field.

Despite this, there continues to be favorable regulatory outcomes and a high demand for novel, on-demand cell and gene therapies. We are seeing progress being made in the development of allogeneic cell banks, and new higher throughput processes are gaining momentum, lowering material costs, and increasing scalability.

We can also expect to leverage the lessons learned from autologous therapies, approved cell and gene therapies, and COVID-19 vaccines, and apply them to the rare disease fields. Allogeneic therapies are poised to be significantly safer for patients and more commercially viable in the rare disease space in the next five to ten years. With efficiencies on the horizon, there is promising potential for rapid development and improvements in clinical research in the cell and gene landscape in a very real way.

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