Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers. We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell ...therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM).
This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM. Lymphodepletion was performed using cyclophosphamide 300 mg/m
. LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 10
cells/kg range, 0.07 to 2.1 × 10
) were infused in 3 separate infusions. The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group.
At data cutoff, 57 patients had received LCAR-B38M CAR T cells. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were reported in 37/57 patients (65%); most common were leukopenia (17/57; 30%), thrombocytopenia (13/57; 23%), and aspartate aminotransferase increased (12/57; 21%). Cytokine release syndrome occurred in 51/57 patients (90%); 4/57 (7%) had grade ≥ 3 cases. One patient reported neurotoxicity of grade 1 aphasia, agitation, and seizure-like activity. The overall response rate was 88% (95% confidence interval CI, 76 to 95); 39/57 patients (68%) achieved a complete response, 3/57 (5%) achieved a very good partial response, and 8/57 (14%) achieved a partial response. Minimal residual disease was negative for 36/57 (63%) patients. The median time to response was 1 month (range, 0.4 to 3.5). At a median follow-up of 8 months, median progression-free survival was 15 months (95% CI, 11 to not estimable). Median overall survival for all patients was not reached.
LCAR-B38M CAR T cell therapy displayed a manageable safety profile and demonstrated deep and durable responses in patients with R/R MM.
ClinicalTrials.gov , NCT03090659 ; Registered on March 27, 2017, retrospectively registered.
Recently, inorganic halide perovskite (CsPbX3, X = Cl, Br, I) quantum dots (QDs) have attracted tremendous research interests because of their great potential for application in the fields of ...low-cost light sources and displays. However, the unsatisfactory structural and chemical stabilities of such materials are the main obstacles hindering reliable device operation significantly. In this study, we successfully prepared CsPbBr3/silica QD composites through a simple sol-gel reaction by using tetramethoxysilane as a single molecule precursor. The as-prepared CsPbBr3/silica QD composites demonstrated substantially improved stability against heat, light, and environmental oxygen/moisture. Besides, a relatively narrower photoluminescence linewidth and higher quantum yield were achieved compared with that of fresh CsPbBr3 QDs. Furthermore, the CsPbBr3 QDs/silica composites were applied as color-converting layer curing on blue light-emitting diodes (LEDs) for white LED applications. Finally, a high power efficiency of 63.5 lm W-1 was obtained and the light emission could be efficiently sustained over 13 h without any decay in the continuous current mode, demonstrating remarkable operation stability than that reported previously. It can be anticipated that the excellent properties and facile processing technique used here will make perovskite QDs/silica composites attractive for applications in optoelectronics and industrial fields.
Biliary tract cancers (BTCs), including cholangiocarcinoma and gallbladder carcinoma, originate from the biliary epithelium and have a poor prognosis. Surgery is the only choice for cure in the early ...stage of disease. However, most patients are diagnosed in the advanced stage and lose the chance for surgery. Early diagnosis could significantly improve the prognosis of patients. Bile has complex components and is in direct contact with biliary tract tumors. Bile components are closely related to the occurrence and development of biliary tract tumors and may be applied as biomarkers for BTCs. Meanwhile, arising evidence has confirmed the immunoregulatory role of bile components. In this review, we aim to summarize and discuss the relationship between bile components and biliary tract cancers and their ability as biomarkers for BTCs, highlighting the role of bile components in regulating immune response, and their promising application prospects.
Identifying novel drug targets to overcome resistance to tyrosine kinase inhibitors (TKIs) and eradicating leukemia stem/progenitor cells are required for the treatment of chronic myelogenous ...leukemia (CML). Here, we show that ubiquitin-specific peptidase 47 (USP47) is a potential target to overcome TKI resistance. Functional analysis shows that USP47 knockdown represses proliferation of CML cells sensitive or resistant to imatinib in vitro and in vivo. The knockout of Usp47 significantly inhibits BCR-ABL and BCR-ABL
-induced CML in mice with the reduction of Lin
Sca1
c-Kit
CML stem/progenitor cells. Mechanistic studies show that stabilizing Y-box binding protein 1 contributes to USP47-mediated DNA damage repair in CML cells. Inhibiting USP47 by P22077 exerts cytotoxicity to CML cells with or without TKI resistance in vitro and in vivo. Moreover, P22077 eliminates leukemia stem/progenitor cells in CML mice. Together, targeting USP47 is a promising strategy to overcome TKI resistance and eradicate leukemia stem/progenitor cells in CML.
Mucosa is a protective and lubricating barrier in biological tissue, which has a great clinical inspiration because of its slippery, soft, and hydrophilic surface. However, mimicking mucosal traits ...on complex surface remains an enormous challenge. Herein, a novel approach to create mucosa‐like conformal hydrogel coating is developed. A thin conformal hydrogel layer mimicking the epithelial layer is obtained by first absorbing micelles, followed by forming covalent interlinks with the polymer substrate via interface‐initiated hydrogel polymerization. The resulting coating exhibits uniform thickness (≈15 µm), mucosa‐matched compliance (Young's modulus = 1.1 ± 0.1 kPa) and lubrication (coefficients of friction = 0.018 ± 0.003), robust interfacial bonding against peeling (peeling strength = 1218.0 ± 187.9 J m–2), as well as high water absorption capacity. It effectively resists adhesion of proteins and bacteria without compromising biocompatibility. As demonstrated by an in vivo cynomolgus monkey model and clinical trial, applications of the mucosa‐like conformal hydrogel coating on the endotracheal tube significantly reduce intubation‐related complications, such as invasive stimuli, mucosal lesions, laryngeal edema, inflammation, and postoperative pain. This work offers a promising prototype for surface decoration of biomedical devices and holds great prospects for clinical translation to enable interventional operations with minimally invasive impacts.
An ingenious yet feasible method of creating a mucosa‐like conformal hydrogel coating, which is soft, lubricative, hydrophilic, antifouling, biocompatible, and stable, is reported. This coating effectively reduces intubation‐related complications. This work represents a breakthrough to endow interventional medical devices with required surface properties, showing promising prospects for clinical translation.
Single-atom catalysts not only maximize metal atom efficiency, they also display properties that are considerably different to their more conventional nanoparticle equivalents, making them a ...promising family of materials to investigate. Herein we developed a general host-guest strategy to fabricate various metal single-atom catalysts on nitrogen-doped carbon (M
/CN, M = Pt, Ir, Pd, Ru, Mo, Ga, Cu, Ni, Mn). The iridium variant Ir
/CN electrocatalyses the formic acid oxidation reaction with a mass activity of 12.9 Formula: see text whereas an Ir/C nanoparticle catalyst is almost inert (~4.8 × 10
Formula: see text). The activity of Ir
/CN is also 16 and 19 times greater than those of Pd/C and Pt/C, respectively. Furthermore, Ir
/CN displays high tolerance to CO poisoning. First-principle density functional theory reveals that the properties of Ir
/CN stem from the spatial isolation of iridium sites and from the modified electronic structure of iridium with respect to a conventional nanoparticle catalyst.
Abstract
Atomic interface regulation is thought to be an efficient method to adjust the performance of single atom catalysts. Herein, a practical strategy was reported to rationally design single ...copper atoms coordinated with both sulfur and nitrogen atoms in metal-organic framework derived hierarchically porous carbon (S-Cu-ISA/SNC). The atomic interface configuration of the copper site in S-Cu-ISA/SNC is detected to be an unsymmetrically arranged Cu-S
1
N
3
moiety. The catalyst exhibits excellent oxygen reduction reaction activity with a half-wave potential of 0.918 V vs. RHE. Additionally, through in situ X-ray absorption fine structure tests, we discover that the low-valent Cuprous-S
1
N
3
moiety acts as an active center during the oxygen reduction process. Our discovery provides a universal scheme for the controllable synthesis and performance regulation of single metal atom catalysts toward energy applications.
Piezoelectric polymers hold great potential for various electromechanical applications, but only show low performance, with |d
| < 30 pC/N. We prepare a highly piezoelectric polymer (d
= -62 pC/N) ...based on a biaxially oriented poly(vinylidene fluoride) (BOPVDF, crystallinity = 0.52). After unidirectional poling, macroscopically aligned samples with pure β crystals are achieved, which show a high spontaneous polarization (P
) of 140 mC/m
. Given the theoretical limit of P
= 188 mC/m
for the neat β crystal, the high P
cannot be explained by the crystalline-amorphous two-phase model (i.e., P
= 270 mC/m
). Instead, we deduce that a significant amount (at least 0.25) of an oriented amorphous fraction (OAF) must be present between these two phases. Experimental data suggest that the mobile OAF resulted in the negative and high d
for the poled BOPVDF. The plausibility of this conclusion is supported by molecular dynamics simulations.
Abstract
Non-retroviral endogenous viral elements (nrEVEs) are widely dispersed throughout the genomes of eukaryotes. Although nrEVEs are known to be involved in host antiviral immunity, it remains ...an open question whether they can be domesticated as functional proteins to serve cellular innovations in arthropods. In this study, we found that endogenous toti-like viral elements (ToEVEs) are ubiquitously integrated into the genomes of three planthopper species, with highly variable distributions and polymorphism levels in planthopper populations. Three ToEVEs display exon‒intron structures and active transcription, suggesting that they might have been domesticated by planthoppers. CRISPR/Cas9 experiments revealed that one ToEVE in
Nilaparvata lugens
, NlToEVE14, has been co-opted by its host and plays essential roles in planthopper development and fecundity. Large-scale analysis of ToEVEs in arthropod genomes indicated that the number of arthropod nrEVEs is currently underestimated and that they may contribute to the functional diversity of arthropod genes.
Inorganic films possess much higher thermoelectric performance than their organic counterparts, but their poor flexibilities limit their practical applications. Here, Sb2Te3/Tex hybrid thin films ...with high thermoelectric performance and flexibility, fabricated via a novel directional thermal diffusion reaction growth method are reported. The directional thermal diffusion enables rationally tuning the Te content in Sb2Te3, which optimizes the carrier density and leads to a significantly enhanced power factor of >20 µW cm–1 K–2, confirmed by both first‐principles calculations and experiments; while dense boundaries between Te and Sb2Te3 nanophases, contribute to the low thermal conductivity of ≈0.86 W m–1 K–1, both induce a high ZT of ≈1 in (Sb2Te3)(Te)1.5 at 453 K, ranking as the top value among the reported flexible films. Besides, thin films also exhibit extraordinary flexibility. A rationally designed flexible device composed of (Sb2Te3)(Te)1.5 thin films as p‐type legs and Bi2Te3 thin films as n‐type legs shows a high power density of >280 µW cm–2 at a temperature difference of 20 K, indicating a great potential for sustainably charging low‐power electronics.
A high ZT of ≈1 at 453 K is achieved in an inorganic Sb2Te3/Te hybrid thin film via a novel directional thermal diffusion reaction growth method with extraordinary flexibility, and the rationally designed flexible device shows a high power density by a low‐temperature difference.
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