Potential roles of hyaluronic acid in in vivo CAR T cell reprogramming for cancer immunotherapy

Chimeric antigen receptor (CAR) T cell therapy has recently shown unprecedented clinical efficacy for cancer treatment, particularly of hematological malignancies. However, the complex manufacturing processes that involve ex vivo genetic modification of autologous T cells limits its therapeutic application. CAR T cells generated in vivo provide a valid alternative immunotherapy, â off-the-shelfâ , for cancer treatment. This approach requires carriers for the delivery of CAR-encoding constructs, which are plasmid DNA or messenger RNA, to T cells for CAR expression to help eradicate the tumor. As such, there are a growing number of studies reporting gene delivery systems for in vivo CAR T cell therapy based on viral vectors and polymeric nanoparticles. Hyaluronic acid (HA) is a natural biopolymer that can serve for gene delivery, because of its inherent properties of cell recognition and internalization, as well as its biodegradability, biocompatibility, and presence of functional groups for the chemical conjugation of targeting ligands. In this review, the potential of HA in the delivery of CAR constructs is discussed on the basis of previous experience of HA-based nanoparticles for gene therapy. Furthermore, current studies on CAR carriers for in vivo-generated CAR T cells are included, giving an idea of a rational design of HA-based systems for the more efficient delivery of CAR to circulating T cells.This research is funded by Chulalongkorn University (grant number: ReinUni_65_03_33_20). Additionally, this research was partially supported by the Asahi Glass Foundation (grant number: RES_65_530_33_026). This research project is supported by the Second Century Fund (C2F), Chulalongkorn University

In vitro polishing effectiveness of interdental aids on root surfaces

. The purpose of this study was: (1) to determine whether polishing standardized proximal root surfaces with dental floss, Superfloss, wood and plastic interdental cleaners, using a polishing paste, produces any significant change on root surface roughness; and (2) to determine the effectiveness of different number of strokes in polishing. 80 tooth specimens were prepared, 10 in each of 8 sample groups. Each proximal root surface was standardized with 600A grit silicone carbide paper and polished with either waxed dental floss, Superfloss, wood or plastic interdental cleaners, using alkali aluminum silicate polishing paste. All specimens were mounted on a flossing machine and polished with 10 or 20 strokes. Before and after polishing, measurements were recorded with the Surfanalyzer 150 System to produce profile and average roughness tracings. Average maximum peak heights, mean number of peaks, and mean average roughness values were calculated from the tracings. The data were analyzed statistically by paired t-test and Student t-test. No significant mean differences were found between the number of strokes used. No significant differences were found for waxed dental floss in relation to the values analyzed. Significant differences were found for maximum peak heights for Superfloss following 20 strokes of polishing. However, no significant differences were found for Superfloss for mean number of peaks and average roughness. Significant differences were found for average roughness values, maximum peak heights, and mean number of peaks for the wood and plastic interdental cleaners. It was concluded that root surface roughness increased significantly with the use of wood and plastic interdental cleaners but not with waxed dental floss or Superfloss.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75532/1/j.1600-051X.1986.tb00853.x.pd