Cell Therapies

Introduction: Process Issues in Cell, Gene, and Tissue Therapies

It’s hard to believe that just six years ago, BioProcess International published its first cell therapy supplement, which included just one article on “cell therapy bioprocessing” (1). At the time, most such processing was conducted in special clinical laboratories and academic institutions. As BPI continued to cover this relatively new segment of the biopharmaceutical industry, we heard more about “the product is the process” and “scale out instead of scaling up.” After many trials, errors, and milestones, regenerative medicine has…

Expansion Platform Components

I first met Chris Mach at the Biotech Week Boston conference in October. We discussed the challenges that biomanufacturers are facing in cell expansion, especially in three specific areas in scale-up systems. Stack Vessels: Mach said many of his company’s customers are currently facing challenges with selecting the right platforms for growing their cells or viruses. He pointed out that stack vessels perform extremely well in different applications (e.g., for cell therapies), and they’re compact and disposable. “Many customers do…

Platform Solutions for Cell Therapy Manufacturing

Advances in cell therapy have resulted in significant progress toward treating some widespread and difficult diseases, many of which represent unmet medical needs. For example, phase 3 clinical trials are already under way for therapies based on mesenchymal stem cells (MSCs), including therapies for graft-versus-host disease, acute myocardial ischemia, and chronic obstructive pulmonary disease (COPD) (1–3). Successful cell therapy treatments for such afflictions will be not only significant medical breakthroughs, but also in very high demand. However, their commercialization is…

Scalable Purification of Viral Vectors for Gene Therapy: An Appraisal of Downstream Processing Approaches

Gene therapy is the transfer of genetic material to a patient’s cells to achieve a therapeutic effect. Therapeutic DNA is largely delivered using viral vector systems based on adenoviruses (Ad), adenoassociated viruses (AAV), and lentiviruses (LV). With the application of such viral vectors as clinical therapeutics growing, scalable commercial processes (particularly for purification) are being investigated and optimized to best ensure that critical quality attributes (CQAs) are retained. Herein we review viral vector purification techniques and the effect of different…

3D Bioprinting Possibilities and Challenges

Three-dimensional (3D) bioprinting is the newest addition to the regenerative medicine family. Now within the industry dedicated to providing more personalized drug products, this new additive-manufacturing technology has the potential to truly focus on individual tissue repair and replacement. In a short period of time, 3D bioprinting has been applied in studies using bones, blood vessels, composite tissues, vascular grafts, tracheal splints, cartilaginous structures, heart tissue (e.g., two-valve heart), and vaginal organs (1). With conference presentations and other studies discussing…

Cell-Delivered Gene Therapy: This Viral Vector Manufacturing Method Could Widen Its Applicability

Cell-delivered gene therapy is making an impact on a range of diseases (1–17). To date, successful treatments have generally been in conditions involving genetic deficiencies/abnormalities, for which introduction of a normal gene allele has been corrective (1–12, 18). Such an approach requires a vector containing the normal allele to overcome the mutant or lacking gene. The vector of choice for cell-delivered gene therapy is often a lentivirus that integrates and expresses introduced therapeutic genes in host target cells and their…

Engineering Tissues with Bioprinting

Commonly referred to as three-dimensional (3D) printing, additive manufacturing encompasses a set of technologies that fabricate objects in an additive way, layer by layer, rather than conventional means of fabrications that generally subtract unwanted material from a larger block. Precise control over material placement allows 3D printing to fabricate objects that otherwise would not be manufacturable. Although many of these technologies have been around for two or three decades, recently they have received a significant amount of attention from industry,…

Progress Toward Commercial Scale and Efficiency in Cell Therapy Bioprocessing

Regenerative medicine includes both cell and gene therapies. Currently 672 regenerative medicine companies operate around the world, and 20 products have been approved by the US Food and Drug Administration (FDA). Of 631 ongoing clinical trials by the end of 2015 (1), over 40% are in oncology, followed in prominence by cardiovascular and infectious diseases. Here I focus on gene and cell therapy bioprocessing in which the final products delivered to patients are cells. Cell therapies are either autologous (derived…

Manufacturing Plasmid DNA: Ensuring Adequate Supplies for Gene and Cell Therapies

The concept of gene therapy is far from new, with initial studies performed over 20 years ago (1). However, in the past few years an explosion of interest in this area has gone beyond initial regenerative approaches using viral vectors. Interest is now moving increasingly into potential use of T cells modified using recombinant viral vectors for immunotherapy applications. Such therapies are based on using either adenoassociated virus (AAV) or lentivirus (1), both vectors being frequently generated through transient expression…

Innovative Downstream Purification Solutions for Viral Vectors: Enabling Platform Approaches to Advance Gene Therapies

Over the past decade, gene therapy applications and their importance in the biopharmaceutical industry have been increasing. Gene therapies promise versatile treatment options that could revolutionize and transform medicine. As treatment modalities, they offer the possibility of long-term and potentially curative benefits to patients with genetic or acquired diseases. Gene therapies are designed to treat disease by delivering genetic material that encodes a protein with a therapeutic effect into a patient’s cells. It can be used to replace a missing…