Bioengineering Solutions for Manufacturing Challenges in CAR T Cells

Abstract

The next generation of therapeutic products to be approved for the clinic is anticipated to be cell therapies, termed “living drugs” for their capacity to dynamically and temporally respond to changes during their production ex vivo and after their administration in vivo. Genetically engineered chimeric antigen receptor (CAR) T cells have rapidly developed into powerful tools to harness the power of immune system manipulation against cancer. Regulatory agencies are beginning to approve CAR T cell therapies due to their striking efficacy in treating some hematological malignancies. However, the engineering and manufacturing of such cells remains a challenge for widespread adoption of this technology. Bioengineering approaches including biomaterials, synthetic biology, metabolic engineering, process control and automation, and in vitro disease modeling could offer promising methods to overcome some of these challenges. Here, we describe the manufacturing process of CAR T cells, highlighting potential roles for bioengineers to partner with biologists and clinicians to advance the manufacture of these complex cellular products under rigorous regulatory and quality control.

Aptamer‐Engineered Natural Killer Cells for Cell‐Specific Adaptive Immunotherapy

“…Under the guidance of surface‐anchored aptamers, ApEn‐NK cells specifically targeted and subsequently induced apoptosis/death of targeted lymphoma cells. This ApEn‐NK platform has several unique features as compared to CAR‐T/NK technology . First, generation of ApEn‐NK cells is a simple, time‐ and labor‐efficient process as it involves a single‐step engineering reaction and can be completed in 30 min.…”

“…However, the genetic manipulation used to generate CAR‐T/NK cells may carry risks for patients, including transgene insertional mutagenesis . Also, the production of CAR‐NK cells is laborious and costly . The development of a simpler and safer technology is necessary to overcome these technical and clinical challenges.…”

CAR T cells for brain tumors: Lessons learned and road ahead

“…Ultimately this process is capable of generating millions to billions of engineered therapeutic CAR T cells ready to be infused back to the patient. A detailed summary of CAR T manufacturing has been reviewed previously . In clinical manufacturing setting of brain tumors, there are many outstanding issues to be addressed, including the following: how intrinsic T cell product variability impacts potency; the effect of concomitant dexamethasone on the quality or quantity of manufactured product; whether certain T cell subsets traffic to the CNS more efficiently; and whether off‐the‐shelf manufacturing platforms will improve the consistency, timing, and availability of CAR T therapy.…”

Characterizing modes of action and interaction for multicomponent osmolyte solutions on Jurkat cells

“…Cell‐based immunotherapies such as chimeric antigen receptor (CAR) T‐cell therapy are increasingly becoming an important means of treating a number of cancers, including certain types of lymphoma and leukemia. In these treatments, immune cells are harvested from patients, genetically modified to better enable them to target cancer cells, and then reinfused into the patients (Piscopo et al, ). Effective preservation of these cells at each stage of the process is critical to clinical use as it enables transportation from the site of collection to the site of manufacture and to the site of use.…”