Risk factors for CAR-T cell manufacturing failure among DLBCL patients: A nationwide survey in Japan

CAR-T細胞製造を成功させるためのレシピ --アフェレーシス前の下ごしらえでの工夫--. 京都大学プレスリリース. 2023-04-27.For successful chimeric antigen receptor T (CAR-T) cell therapy, CAR-T cells must be manufactured without failure caused by suboptimal expansion. In order to determine risk factors for CAR-T cell manufacturing failure, we performed a nationwide cohort study in Japan and analysed patients with diffuse large B-cell lymphoma (DLBCL) who underwent tisagenlecleucel production. We compared clinical factors between 30 cases that failed (7.4%) with those that succeeded (n = 378). Among the failures, the proportion of patients previously treated with bendamustine (43.3% vs. 14.8%; p < 0.001) was significantly higher, and their platelet counts (12.0 vs. 17.0 × 10⁴/μL; p = 0.01) and CD4/CD8 T-cell ratio (0.30 vs. 0.56; p < 0.01) in peripheral blood at apheresis were significantly lower than in the successful group. Multivariate analysis revealed that repeated bendamustine use with short washout periods prior to apheresis (odds ratio [OR], 5.52; p = 0.013 for ≥6 cycles with washout period of 3–24 months; OR, 57.09; p = 0.005 for ≥3 cycles with washout period of <3 months), low platelet counts (OR, 0.495 per 105/μL; p = 0.022) or low CD4/CD8 ratios (<one third) (OR, 3.249; p = 0.011) in peripheral blood at apheresis increased the risk of manufacturing failure. Manufacturing failure remains an obstacle to CAR-T cell therapy for DLBCL patients. Avoiding risk factors, such as repeated bendamustine administration without sufficient washout, and risk-adapted strategies may help to optimize CAR-T cell therapy for DLBCL patients

Flattening and manipulation of the electronic structure of h-BN/Rh(111) nanomesh upon Sn intercalation

We have deposited Sn on corrugated hexagonal boron nitride (h-BN) nanomeshs formed on Rh(111) and found that Sn atoms are intercalated between h-BN and Rh, flattening the h-BN. Our reflection high-energy electron diffraction (RHEED) analysis showed that the average in-plane lattice constant of h-BN increases due to the loss of the corrugation. Furthermore, electronic structure measurements based on angle-resolved photoemission spectroscopy (ARPES) showed that the h-BN π band width increases significantly while the σ band width does not change as much. These behaviors were partly different from previous reports on the intercalation of h-BN/Rh system. Our results offer a novel, simple method to control the electronic structure of h-BN

Biosorption of Tungsten by <i>Escherichia coli</i> for an Environmentally Friendly Recycling System

In this study, tungsten (W) recovery via biosorption using <i>Escherichia coli</i> was assessed to establish an environmentally friendly recycling system for W. The recovery fraction of soluble W^VI was highly dependent on the solution pH, and <i>E. coli</i> cells exhibited the highest W^VI uptake capacity for an initial pH of 1.08–2.56. Fourier transform infrared analysis revealed that carboxyl and phosphate functional groups on the surface of the bacteria play a crucial role in adsorption of W^VI. Equilibrium and kinetic modeling of W^VI biosorption showed that the equilibrium adsorption data fit the Langmuir isotherm model better than the Freundlich model. Kinetic studies revealed that W^VI adsorption followed a pseudo-second-order rate model. W^VI was recovered by desorption and heating, and adjustment of the pH enabled 95.8% W^VI desorption from the <i>E. coli</i> cells. Heating at 1000 °C for 2 h under atmospheric conditions produced concentrates with relatively high concentrations of W^VI (97.1% WO₃)