|When Considering Cell Therapy Investments - Not All Cells Are the Same Q&A with Zami Aberman, Pluristem Therapeutics|
|Wednesday, 17 December 2014 19:54|
Garza: What is the importance of the type of tissue used as a source for cells?
The tissue source can be important in many ways. For example, mesenchymal stem cells can be harvested from multiple tissues including bone marrow, fat and placental tissue. The placenta provides cells from the youngest non-embryonic source, while cells harvested from the bone marrow or fat are generally taken from an adult who may potentially have had a history of exposure to environmental toxins or infections across their lifetime. The placenta is also a very good raw material because it is a rich source of mesenchymal stem cells and is usually discarded after birth. That means that it can be collected easily without the need for an invasive procedure, as is generally used for bone marrow or fat collection. At Pluristem we use cells from placental tissue collected at a scheduled cesarean section, giving us the opportunity to properly consent and screen the mother before her delivery.
Garza: Tell us more about placental cells and why Pluristem has chosen to develop cell therapies derived from these cells.
The placenta is a particularly rich source for therapeutic cells. It is a uniquely immunoprivileged site in the body, because it manages the interaction between the mother’s and fetus’ cells, which differ in half their DNA; in the case of surrogacy the DNA of the mother and fetus differs completely. Certain placental cells, as a result, are far less likely to trigger an immune reaction than most other cells. This makes it possible to inject a cell product derived from one placenta into different people without the need for tissue matching.
Garza: Pluristem is known in the industry for its unique 3-D cell expansion technologies and cell manufacturing methods. Why should cell expansion and processing technologies determine the characteristics of cells being developed as therapeutic products?
Cells are sensitive to the environment and techniques used to grow or modify them. Any change in the process that affects a cell’s environment can change gene expression via epigenetic processes. Those processes are how environment can affect a cell’s development without changing its DNA. In some cases certain changes in a cell’s environment can modify the qualities of cells, such as which proteins they secrete. One can inadvertently modify cells by making small changes in a manufacturing process. The resulting product could have different efficacy or potency than was intended. That is why a controlled environment is needed to grow and develop therapeutic cells.
In order to achieve the necessary level of consistency in its manufactured products a company needs to find a way to ensure batch-to-batch consistency prior to embarking on clinical trials. A technology platform and a manufacturing process must be precisely controlled and stable in order to be capable of producing the same product consistently for clinical trials and potentially for commercialization. Without batch-to-batch consistency for a cell product the chances for accurate clinical trials are reduced, as is the certainty that all patients are receiving the same product at the expected potency.
Garza: What is the long term impact of a rigorous, exacting technology platform and manufacturing process on cell products?
Cells that are made using exact, consistent methods can potentially reliably produce the same cell product as the one that was optimized during product development. An inconsistent manufacturing process cannot assure that a cell product produced in large quantities is the same that was originally developed by researchers. Regarding mesenchymal-like stem cells this is most clinically relevant in terms of their secretion profile of therapeutic proteins thought to trigger healing in the body. Translation of science from bench to bedside is only possible if the necessary steps are taken to ensure the consistency and functionality of cell therapy products.
Garza: Once manufactured, what is the shelf-life of these cells and are there challenges around storage and one-site use?
In allogenic therapy, in which therapeutic cells made from one donor source can be manufactured and stored for eventual administration to multiple patients without the need for tissue matching, there must also be the ability to store cells for long periods. This confers the clear advantage to an allogenic model. The business model for allogenic therapy includes the need for “off-the-shelf” availability of cells. Manufacturing processes must reliably generate cells that can retain efficacy and potency when retrieved from storage. Without this capability trials and treatments can be compromised. Concentrations of live cells must also be consistent from dose to dose so that proper dosing and effectiveness is possible. At Pluristem we freeze our cells and can store them for a minimum of 18 months; we anticipate that this period can be longer. We have successfully stored our cells in 5 different countries to supply clinical trials. There must be a consistent, systematic way to thaw cells that were frozen for storage, and this must be doable at the point of care just before administration. For this purpose, we’ve developed a thawing device that thaws a vial of our PLX cells in 6 minutes, in a standardized and quality-controlled process. A common method for thawing cells, however, is the use of a warm water bath. This can be difficult to standardize and ensure uniform potency for different batches of cells.
Garza: There are a number of cell therapy companies developing products right now. Some have had initial success with their clinical trials, and others have not. What differentiates Pluristem and its cells in the industry?
First off, we wish all our colleagues well. Their success is ours in the sense of moving the cell therapy space forwards. Pluristem is different in several key ways. We believe that by sourcing our cells from the placenta we minimize potential pitfalls for cell therapy products including potential immune rejection by the host or difficulties in acquiring a tissue source. We also believe that technology platform and manufacturing processes must be optimized early on in the development process in order to produce cell therapy products that could be suitable for patient treatment. We chose to optimize our manufacturing methods, and our facility, which is FDA and EMA approved, early on in the process in order to be ready to reliably scale up production as needed for trials or commercialization. Our advanced manufacturing technology enables us to precisely program our cells to secrete specific proteins to treat a specific indication, meaning that our technology platform allows us to develop different products for different indications. We currently have two distinct products in trials and are developing additional ones.