Yi Chun Kuo

Chimeric antigen receptor (CAR) T cell therapies have transformed treatment of B cell malignancies. However, their broader application is limited by complex manufacturing processes and the necessity for lymphodepleting chemotherapy, restricting patient accessibility. We present an in vivo engineering strategy using targeted lipid nanoparticles (tLNPs) for messenger RNA delivery to specific T cell subsets. These tLNPs reprogrammed CD8 + T cells in both healthy donor and autoimmune patient samples, and in vivo dosing resulted in tumor control in humanized mice and B cell depletion in cynomolgus monkeys. In cynomolgus monkeys, the reconstituted B cells after depletion were predominantly naïve, suggesting an immune system reset. By eliminating the requirements for complex ex vivo manufacturing, this tLNP platform holds the potential to make CAR T cell therapies more accessible and applicable across additional clinical indications.

Outsourcing is used to alleviate capacity shortages and increase production flexibility. Generally, the outsourcing decision of manufacturing processes is determined by the capacity utilization rate and focus on individual process. In this article, multicriteria are considered by applying the data envelopment analysis to evaluate the relative efficiencies of all the manufacturing processes to help to assess the allocation of a company's resources. The Malmquist productivity index (MPI) is further employed to measure the productivity changes of each process, on which the outsourcing decision can be based. The empirical case of a Taiwanese printed circuit board manufacturer is applied to illustrate the outsourcing decision process. According to the outsourcing decision matrix proposed in this article, the manufacturing process with low efficiency score and MPI value was identified as a high priority for outsourcing. The outcome shows that the manufacturing process with a higher investment of fixed assets does not guarantee better efficiency. If a company follows the outsourcing decision suggested by the proposed approach, the capacity utility rate and the production quantity per person can be increased. The results and analysis model can provide an alternative for managerial thinking and practical application for outsourcing decisions.

BACKGROUND: AZOOR was first described by Gass in 1993 as a syndrome with rapid loss of one or more extensive zones of the outer retinal segments. It is characterized by photopsia, minimal funduscopic changes, and electroretinographic abnormalities. The efficacy of systemic steroids in treating AZOOR has been previously described and advocated by the concept of autoimmune retinopathy. However, the use of intravitreal of sustained-released steroid had not been mentioned to date. CASE PRESENTATION: A 34-year-old man had sudden onset of central scotoma and photopsia in the left eye. His visual acuity continued deteriorating. The visual field defect demonstrated bilateral enlarged blind spots and altitudinal defects. Fluorescein angiography (FA) showed nonspecific retinal inflammation, and an electroretinogram (ERG) illustrated decreased amplitude of the b wave in both eyes. Optical coherence tomography (OCT) examinations revealed parafoveal loss of the photoreceptor inner/outer segment (IS/OS) junction. Therefore, acute zonal occult outer retinopathy (AZOOR) was diagnosed. Although his vision did not improve under the initial treatment of systemic corticosteroid and calcium channel blocker, remarkable improvement was noticed after the intravitreal injection(IVI) of Ozurdex, consistent with the recovered IS/OS junction disruption. CONCLUSIONS: We herein report a typical case of AZOOR, suggesting that the intravitreal injection of steroid may benefit in certain patients.