Use of Chimeric Antigen Receptor T Cell Therapy in Clinical Practice for Relapsed/Refractory Aggressive B Cell Non-Hodgkin Lymphoma: An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy.

Axicabtagene ciloleucel (YESCARTA; Kite Pharma, a Gilead Company, Los Angeles CA) and tisagenlecleucel (KYMRIAH; Novartis Pharmaceuticals Corp., Basel, Switzerland) are two CD19-directed chimeric antigen receptor (CAR) T cell products currently approved by the US Food and Drug Administration; the European Medicines Agency; Health Canada; Ministry of Health, Labor and Welfare (Japan); and Therapeutic Goods Administration (Australia) for treatment of specific subtypes of relapsed/refractory aggressive B cell non-Hodgkin lymphoma (NHL). Although this approval has been transformative in the use of cellular immunotherapy in lymphoma, there are concerns regarding appropriate use of this novel therapy and of short- and long-term toxicities. To address these issues, representatives of the American Society of Transplantation and Cellular Therapy convened to recognize and address key issues surrounding the clinical application of CD19 CAR T cell therapy in B cell lymphomas, in collaboration with worldwide experts. The aim of this article is to provide consensus opinion from experts in the fields of hematopoietic cell transplantation, cellular immunotherapy, and lymphoma regarding key clinical questions pertinent to the use of CD19 CAR T cell products for the treatment of NHL. As the clinical practice using CAR T cells grows worldwide, we anticipate that this guidance will be relevant for hematology/oncology physicians who care for patients with lymphomas.

Osmolyte-induced folding enhances tryptic enzyme activity.

Osmolytes form a class of naturally occurring small compounds known to protect proteins in their native folded and functional states. Among the osmolytes, trimethylamine-N-oxide (TMAO) has received special interest lately because it has shown an extraordinary capability to support folding of denatured to native-like species, which show significant functional activity. Most enzymes and/or proteins are commonly stored in glycerol to maintain their activity/function. In the present study, we tested whether TMAO can be a better solute than glycerol for two commonly used proteases, trypsin and chymotrypsin. Our enzyme kinetic data suggest that the enzyme activity of trypsin is significantly enhanced in TMAO compared to glycerol, whereas chymotrypsin activity is not significantly changed in either case. These results are in accordance with the osmolyte effects on the folding of these enzymes, as judged by data from fluorescence emission spectroscopy. These results suggest that TMAO may be a better solute than glycerol to maintain optimal tryptic enzyme activity.