Cell-based therapy technology classifications and translational challenges

Abstract

Cell therapies offer the promise of treating and altering the course of diseases which cannot be addressed adequately by existing pharmaceuticals. Cell therapies are a diverse group across cell types and therapeutic indications and have been an active area of research for many years but are now strongly emerging through translation and towards successful commercial development and patient access. In this article, we present a description of a classification of cell therapies on the basis of their underlying technologies rather than the more commonly used classification by cell type because the regulatory path and manufacturing solutions are often similar within a technology area due to the nature of the methods used. We analyse the progress of new cell therapies towards clinical translation, examine how they are addressing the clinical, regulatory, manufacturing and reimbursement requirements, describe some of the remaining challenges and provide perspectives on how the field may progress for the future.

Keywords: cell therapy; clinical trial; manufacturing; regulation; reimbursement; translation.

Figure 1.

Illustration of cell-technology classification in relation to potential therapeutic use. Key: long arrow towards the human body indicates an autologous approach; short arrows indicate the potential for allogeneic approaches; dashed arrow indicates combinatorial use of cells in 3D technologies; GM stands for gene modifications. The bubbles accompanying each classification graphically illustrate specific technology characteristics as follows: Ex vivo GM with viral vectors: a somatic cell and a generic lentivirus enclosing a vector containing a gene sequence of interest; Somatic cells: a flow cytometry diagram, a method often used to purify or characterize somatic cells prior to usage based on cell surface marker expression; In vivo GM with viral vectors: a generic adenovirus enclosing a vector containing a gene sequence of interest; 3D technologies: a trachea exemplifying a biological three-dimensional scaffold; Cell immortalization: a generic cell and the molecular structure of 4-hydroxytamoxifen, a compound used as an immortalization regulator; Genome editing: a scissor cutting a DNA strand; Cell plasticity: a pluripotent stem cell differentiation tree symbolizing cell plasticity.

Figure 2.

Cost-based manufacturing development model. The reimbursement point is the keystone from which an allowable COGs is determined by subtracting business costs. Manufacturing cost models and associated production technology options can then be systematically investigated to deliver suitable productivity at an allowable batch cost, compatible with the reimbursement strategy.

Figure 3.

Manufacturing process choices for scale out and scale up of cell technologies. Both the scale of production and the cell-technology type have a significant impact on the production processes used to generate the product. Small scale, patient-specific therapies are commercialized by scaling-out the same process. By contrast, allogeneic therapies are amendable to scale up, which can deliver many identical doses at larger production volumes. Some cell technologies, such as cell plasticity are currently transitioning from small scale-out systems to larger volume scale up production methods.

Figure 4.

Flowchart for NHS adoption of licensed cell therapies in England. Multiple market access stakeholders are involved in determining NHS adoption. The relative importance of these stakeholders varies by type of cell therapy.