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1.
Small ; : e2311671, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38544302

RESUMO

Energy-efficient white light-emitting diodes (LEDs) are in high demand across the society. Despite the significant advancements in the modern lighting industry based on solid-state electronics and inorganic phosphor, solid-state lighting (SSL) continues to pursue improved efficiency, saturated color performance, and longer lifetime. Here in this article, robust, narrow emission band nanorods (NRs) are disclosed with tailored wavelengths, aiming to enhance the color rendering index (CRI) and luminous efficacy (LE). The fabricated lighting device consists of NRs of configuration CdSe/ZnxCd1-xS/ZnS, which can independently tune CRI R1-R9 values and maximize the luminous efficacy. For general lighting, NRs with quantum yield (QY) up to 96% and 99% are developed, resulting in ultra-efficient LEDs reaching a record high luminous efficacy of 214 lm W-1 (certified by the National Accreditation Service). Furthermore, NRs are deployed onto mid-power (0.3 W@ 50 mA) LEDs, showing significantly enhanced long-term stability (T95 = 400 h @ 50 mA). With these astonishing properties, the proposed NRs can pave the way for efficient lighting with desired optical spectrum.

2.
Adv Mater ; 35(47): e2303950, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37749922

RESUMO

Quantum dot (QD) light-emitting diodes (QLEDs) have attracted extensive attention due to their high color purity, solution-processability, and high brightness. Due to extensive efforts, the external quantum efficiency (EQE) of QLEDs has approached the theoretical limit. However, because of the efficiency roll-off, the high EQE can only be achieved at relatively low luminance, hindering their application in high-brightness devices such as near-to-eye displays and lighting applications. Here, this article reports an ultralow roll-off QLED that is achieved by simultaneously blocking electron leakage and enhancing the hole injection, thereby shifting the recombination zone back to the emitting QDs layer. These devices maintain EQE over 20.6% up to 1000 mA cm-2 current density, dropping only by ≈5% from the peak EQE of 21.6%, which is the highest value ever reported for the bottom-emitting red QLEDs. Furthermore, the maximum luminance of the optimal device reaches 320 000 cd m-2 , 2.7 times higher than the control device (Lmax : 128 000 cd m-2 ). A passive matrix (PM) QLED display panel with high brightness based on the optimized device structure is also demonstrated. The proposed approach advances the potential of QLEDs to operate efficiently in high-brightness scenarios.

3.
Nat Astron ; 7(7): 856-866, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37483848

RESUMO

The solar corona is two to three orders of magnitude hotter than the underlying photosphere, and the energy loss of coronal plasma is extremely strong, requiring a heating flux of over 1,000 W m-2 to maintain its high temperature. Using the 1.6 m Goode Solar Telescope, we report a detection of ubiquitous and persistent transverse waves in umbral fibrils in the chromosphere of a strongly magnetized sunspot. The energy flux carried by these waves was estimated to be 7.52 × 106 W m-2, three to four orders of magnitude stronger than the energy loss rate of plasma in active regions. Two-fluid magnetohydrodynamic simulations reproduced the high-resolution observations and showed that these waves dissipate significant energy, which is vital for coronal heating. Such transverse oscillations and the associated strong energy flux may exist in a variety of magnetized regions on the Sun, and could be the observational target of next-generation solar telescopes.

4.
Front Microbiol ; 13: 916488, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910633

RESUMO

The breaking silence between the plant roots and microorganisms in the rhizosphere affects plant growth and physiology by impacting biochemical, molecular, nutritional, and edaphic factors. The components of the root exudates are associated with the microbial population, notably, plant growth-promoting rhizobacteria (PGPR). The information accessible to date demonstrates that PGPR is specific to the plant's roots. However, inadequate information is accessible for developing bio-inoculation/bio-fertilizers for the crop in concern, with satisfactory results at the field level. There is a need to explore the perfect candidate PGPR to meet the need for plant growth and yield. The functions of PGPR and their chemotaxis mobility toward the plant root are triggered by the cluster of genes induced by the components of root exudates. Some reports have indicated the benefit of root exudates in plant growth and productivity, yet a methodical examination of rhizosecretion and its consequences in phytoremediation have not been made. In the light of the afore-mentioned facts, in the present review, the mechanistic insight and recent updates on the specific PGPR recruitment to improve crop production at the field level are methodically addressed.

5.
Nanoscale ; 14(22): 8060-8068, 2022 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35608246

RESUMO

Inorganic multicolour perovskite nanocrystals (NCs) of CsPbX3 (X = Cl, Br, I) with high photoluminescence (PL) quantum yield (QY) and saturated colours are considered promising candidates for a high-performance colour conversion layer. However, integration of these materials into industrial applications still faces a significant challenge due to their tendency for aggregation and quenching of the emission during deposition and processing. In this work, we explore a new ink composition with oleylamine (OLA) and hexylphosphonic acid (HPA) ligands in combination with a liquid crystal monomer (LCM) composing a superior solution for an inkjet-printed colour conversion layer. This work provides a simple technique for preparing high-quality perovskite pixels for high-performance displays.

6.
ACS Appl Mater Interfaces ; 14(16): 18723-18735, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35417119

RESUMO

Solution-processed semiconductor nanocrystals are evolving as potential candidates for future display and lighting applications owing to their size-tunable emission, ultrasaturated colors, and compatibility with large-area flexible substrates. Among them, quantum rods (QRs) are emerging materials for optoelectronic applications, offering polarized emission, high light outcoupling efficiency, color purity, and better stability in solid films. However, synthesizing QRs covering the full visible wavelength region has been a big challenge, particularly in the blue range. Herein, we report for the first time the synthesis of red CdSe/CdS, green CdSe/ZnxCd1-xS/ZnS, and blue CdSe/ZnxCd1-xS/ZnS QRs and their application in red, green, and blue QR-based light-emitting diodes (QR-LEDs). We have improved the charge injection balance into the QRs through embedding a poly(methyl methacrylate) (PMMA) layer between the emissive and electron transport layers. The thin PMMA electron-blocking layer (EBL) suppresses the excessive electron flux and thus promotes charge injection balance and pushes the recombination zone back to the QR layer, resulting in 1.35×, 1.2×, and 1.7× peak external quantum efficiency improvement for red, green, and blue QR-LEDs, respectively. The efficiency roll-off of green and blue QR-LEDs with an EBL is less than 50% at maximum current density. The proposed red, green, and blue QR-LEDs open up an avenue toward further improving the light source efficiency and stability focusing on real device applications.

7.
J Biomol Struct Dyn ; 40(24): 13412-13431, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34696688

RESUMO

SGK1 (Serum and Glucocorticoid Regulated Kinase 1), a serine/threonine kinase that is activated by various stimuli, including serum and glucocorticoids. It controls inflammation, apoptosis, hormone release, neuro-excitability and cell proliferation, all of which play an important role in cancer progression and metastasis. SGK1 was recently proposed as a potential drug target for cancer, diabetes, and neurodegenerative diseases. In this study, molecular docking, physiochemical, toxicological properties and molecular dynamic simulation of the Bis-[1-N,7-N, Pyrazolo tetraethoxyphthalimido{-4-(3,5-Dimethyl-4-(spiro-3-methylpyazolo)-1,7-dihydro-1H-dipyrazolo[3,4-b;4',3'-e]pyridin-8-yl)}]p-disubstituted phenyl compoundsand reference EMD638683 against new SGK1 target protein. Compared to the reference inhibitor EMD638683, we choose the best compounds (series 2-6) based on the binding energy (in the range from -11.0 to -10.6 kcal/mol). With the exception of compounds 2 and 6, none of the compounds posed a risk for AMES toxicity or carcinogenicity due to their toxicological properties. 100 ns MD simulation accompanied by MM/PBSA energy calculations and PCA. According to MD simulation results, the binding of compounds 3, 4 and 5 stabilizes the SGK1 structure and causes febrile conformational changes compared to EMD638683. As a result of this research, the final selected compounds 3, 4 and 5 can be used as scaffolds to develop promising SGK1 inhibitors for the treatment of related diseases such as cancer.Communicated by Ramaswamy H. Sarma.


Assuntos
Benzamidas , Proteínas Serina-Treonina Quinases , Simulação de Acoplamento Molecular , Proteínas Serina-Treonina Quinases/química , Benzamidas/farmacologia , Simulação de Dinâmica Molecular
8.
J Biomol Struct Dyn ; 40(21): 10561-10577, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34243699

RESUMO

Methicillin-Resistant Staphylococcus aureus (MRSA), a pathogenic bacterium that causes life-threatening outbreaks such as community-onset and nosocomial infections as emerging 'superbug'. Time and motion study of its virulent property developed resistance against most of the antibiotics such as Vancomycin. Thereby, to curb this problem entails the development of new therapeutic agents. Plant-derived antimicrobial agents have recently piqued people's interest, so in this research, 186 flavonoids compound selected to unmask the best candidates that can act as potent inhibitors against the Penicillin Binding Protein-2a (PBP-2a) of MRSA. Molecular docking performed using PyRx and GOLD suite to determine the binding affinities and interactions between the phytochemicals and the PBP-2a. The selected candidates strongly interact with the different amino acid residues. The 30 ns molecular dynamics (MD) simulations with five top-ranked compounds such as Naringin, Hesperidin, Neohesperidin, Didymin and Icariin validated the docking interactions. These findings are also strongly supported by root-mean-square deviation, root-mean-square fluctuation and the radius of gyration. ADME/T analysis demonstrates that these candidates appear to be safer inhibitors. Our findings point to natural flavonoids as a promising and readily available source of adjuvant antimicrobial therapy against resistant strains in the future.Communicated by Ramaswamy H. Sarma.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Flavonoides/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Proteínas de Ligação às Penicilinas/química
9.
Bull Environ Contam Toxicol ; 108(3): 468-477, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33860803

RESUMO

The soil samples of old Zawar mine sites were sandy texture, basic, electric conductivity range from 16 to 59 dSm-1 with a high content of heavy metals of Zn, Pb, Cd, and Fe, indicating poor soil-health. Two bacterial isolates Pseudomonas aeruginosa HMR1 and P. aeruginosa HMR16 (GenBank-accession-number KJ191700 and KU174205, respectively), differed in the Phylogenetic tree based on 16S-rDNA sequences. HMR1 isolate showed the high potential of Plant growth-promoting attributes like IAA, Phosphate-solubilization, Exopolysaccharide production, and Proline activities at high concentration of Zn augmented nutrient media after 24 h, followed by HMR1 + HMR16 and HMR16. Both isolates were survived at 100 ppm Zn (w/v) concentration, followed by Pb, Cd, and Fe. Linear RL value from Langmuir and Freundlich isotherms revealed that the suitable condition of Zn adsorption by HMR1 was at pH8 with 40°C. The value of r2 from pseudo-second-order kinetics and Transmission-Electron-Microscopic analysis confirmed Zn adsorption by HMR1.


Assuntos
Metais Pesados , Poluentes do Solo , Metais Pesados/análise , Filogenia , Pseudomonas aeruginosa , Solo , Poluentes do Solo/análise , Zinco/análise
10.
Adv Mater ; 33(49): e2104685, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34632633

RESUMO

Efficient white light-emitting diodes (LEDs) with an efficacy of 200 lm W-1 are much desirable for lighting and displays. The phosphor-based LEDs in use today for display applications offer poor color saturation. Intensive efforts have been made to replace the phosphor with quantum-dot-based downconverters, but the efficiency and stability of these devices are still in their infancy. Quantum rods (QRs), nanoparticles with an elongated shape, show superior properties such as relatively larger Stokes shifts, polarized emission, and high light out-coupling efficiency in the solid-state. However, these QRs usually suffer from poor optical quality for PL wavelengths < 550 nm. Herein, a gradient alloyed CdSe/Znx Cd1- x S/ZnS and CdSe/CdS/ZnS core/shell/shell QR downconverters showing high efficacy LEDs covering a wide color gamut are reported. These QRs show high stability and a precisely tunable photoluminescence peak. The engineered shell thickness suppresses energy transfer and thus maintains the high quantum yield in the solid-state (81%). These QR-based LEDs attain an efficacy of 149 lm W-1 (@10mA) and wide color gamut (118% NTSC), which is exceedingly higher than state-of-the-art quantum dots and phosphor-based on-chip LEDs.

11.
Transfus Apher Sci ; 60(6): 103224, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34366234

RESUMO

The COVID-19 pandemic resulted in multiple waves of infection worldwide. The large variations in case fatality rate among different geographical regions suggest that the human susceptibility against this virus varies substantially. Several studies from different parts of the world showed a significant association of ABO blood group and COVID-19 susceptibility. It was demonstrated that individuals with blood group O are at the lower risk of coronavirus infection. To establish the association of ABO blood group in SARS-CoV-2 susceptibility, we for the first time analysed SARS-CoV-2 neutralising antibodies among 509 individuals, collected from three major districts of Eastern Uttar Pradesh region of India. Interestingly, we found neutralising antibodies in a significantly higher percentage of people with blood group AB (0.36) followed by B (0.31), A (0.22) and lowest in people with blood group O (0.11). We further estimated that people with blood group AB are at comparatively higher risk of infection than other blood groups. Thus, among the asymptomatic SARS-CoV-2 recovered people blood group AB has highest, whilst individuals with blood group O has lowest risk of infection.


Assuntos
Sistema ABO de Grupos Sanguíneos/sangue , COVID-19 , SARS-CoV-2/metabolismo , COVID-19/sangue , COVID-19/epidemiologia , Suscetibilidade a Doenças , Feminino , Humanos , Índia/epidemiologia , Masculino , Pandemias , Fatores de Risco , Índice de Gravidade de Doença
12.
Opt Express ; 29(9): 13978-13986, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33985124

RESUMO

Low-voltage fast switchable 1D and 2D Fibonacci grating (FbG), using an electrically suppressed helix ferroelectric liquid crystal (ESHFLC), with high diffraction efficiency for a super-resolution imaging system in far-field are disclosed in this paper. Specifically, the polarization-independent two-domain (0, π) structure is well designed based on photoalignment technology to maximize the total diffraction efficiency that can reach 97.4% (1st order:8.5%, 2nd order: 30%). Apart from that, the FLC gratings offer two tunable states: non-diffractive and diffractive states. Derived from the fast-response property of ferroelectric liquid crystal material, the switching speed of the 1D and 2D ESHFLC-FbG is 103µs at 4 V of the driving voltage. Furthermore, this system achieves the high-resolving power of (λ/2.25) for object detection based upon the intensity map received behind 1D ESHFLC-FbG at far-field. Contribution from the quasi-periodic FbG's special ability to translate the super-resolution information (including at evanescent wave) into the detectable far-field region. Concisely, the proposed ESHFLC-FbG can be a promising candidate for a super-resolution imaging system, superstructure fibre sensor, and other photonic applications.

13.
Opt Express ; 29(6): 8258-8267, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33820275

RESUMO

Optical devices like virtual reality (VR) headsets present challenges in terms of vergence-accommodation conflict that leads to visual fatigue for the user over time. Lenses available to meet these challenges include liquid crystal (LC) lenses, which possess a response time in the millisecond range. This response time is slow, while accessing multiple focal lengths. A ferroelectric liquid crystal (FLC) has a response time in the microsecond range. In this article, we disclose a switchable lens device having a combination of the fast FLC-based polarization rotation unit and a passive polarization-dependent LC lens. A cascaded combination of three such lens units allows access to eight different focal points quite rapidly and can be a convenient device for VR applications.

14.
Nanoscale ; 13(13): 6400-6409, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33537691

RESUMO

Cesium-lead halide perovskite nanoparticles are a promising class of luminescent materials for color and efficient displays. However, material stability is the key issue to solve before we can use these materials in modern displays. Encapsulation is one of the most efficient methods that can markedly improve the stability of perovskite nanoparticles against moisture, heat, oxygen, and light. Thus, we urgently need a low-cost, reliable, and device-compatible encapsulation method for the integration of nanomaterials into display devices. Here, we propose a facile encapsulation method to stabilize perovskite nanoparticles in thin polymer porous films. Using porous polymer films, we achieved good photoluminescence stability in the harsh environment of high temperature, high humidity and strong UV illumination. The good UV stability benefitted from the unique optical properties of the porous film. Besides, we observed photoluminescence enhancement of CsPbBr3 nanoparticle films in a high humidity environment. The stable CsPbBr3 nanoparticle thin porous film provides high brightness (236 nits) and great color enhancement for LCDs and is characterized by simple fabrication with easy scalability, thus it is very suitable for modern LCDs.

15.
Small ; 17(3): e2004487, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33345459

RESUMO

Recently, quantum rods (QRs) have been studied heavily for display and lighting applications. QRs offer serious advantages over the quantum dots such as higher light out-coupling coefficient, and polarized emission. The QR enhancement films double liquid crystal display efficiency. However, it is still a challenge to synthesize good quality green (λem  ≈ 520 nm) and blue (λem  ≈ 465 nm) emitting QRs, due to very large bathochromic shift during the shell growth. Furthermore, until now, the presence of cadmium in high-quality QRs is inevitable, but due to its toxicity, RoHS has restricted the amount of cadmium in consumer products. In this article, low Cd core-shell QRs, with a narrow-band luminescence spectrum tuned in the whole visible range, are prepared by replacing Cd with Zn in a one-pot post-synthetic development. These QRs possess the good thermal stability of photoluminescence properties, and therefore, show high performance for the on-chip LED configuration. The designed white LEDs (WLEDs) are characterized by a high brightness of 120000 nits, and color gamut covering 122% NTSC (90% of BT2020), in the 1931CIE color space. Additionally, these LEDs show a high luminous efficiency of 115 lm W-1 . Thus, these quantum rod LED are perfectly viable for display backlighting and lighting applications.

16.
Chemosphere ; 267: 129216, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33340884

RESUMO

The present study has focused on the evaluation of the maximum amount of flyash (FA) utilization augmentation in the acidic soil (pH 6.1) with the manure during the growth performance and impact of toxic heavy metals under the pot experiment. The 15 days pre-incubated 40% FA treated combination (T16) significantly (P < 0.05) influenced growth performance of chickpea plant after 60 days. The dry weight as well as the contents of N, P, and K increased from 38.8 to 78.53%, 118 to 86%, 148 to 115%, and 95.8 to 95%, respectively, over control in T15 combination after 30 and 60 days. T15 and T16 both treatments induced a significant rise in IAA and GB from 76 to 75.5% and 50%-45%, respectively, after 60 days. The significant increase in the activities of SOD, APX, CAT, and GR with 47%, 56%, 42%, and 28%, respectively, over control was observed in T16 treated combination after 60 days. The significant (P < 0.05) influence in the antioxidant activities, levels of GB, Proline, TSS, and RS were observed across the treatments and durations. The levels of BCF and TF both were <1 in T16 treated plants for toxic heavy metals (Pb, Mo, Cd, and Al), which indicated a negligible extent of translocation from root to shoot and shoot to edible parts in the plants. The results demonstrated that 40% FA supplementation with manure could induce the growth of chickpea in slightly acidic soil and reduce the translocation of toxic metals in the edible parts of the plant.


Assuntos
Cicer , Metais Pesados , Poluentes do Solo , Antioxidantes , Cinza de Carvão , Hormônios , Metais Pesados/análise , Solo , Poluentes do Solo/análise , Poluentes do Solo/toxicidade
17.
Adv Sci (Weinh) ; 6(22): 1901345, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31763144

RESUMO

Herein, emerging applications of luminescent semiconductor nanocrystals are addressed, such as quantum dots and quantum rods as down-conversion materials used in liquid crystal displays (LCD). Their precisely tunable emission wavelengths and narrow emission bandwidths offer high color purity resulting in a wide color gamut with vivid colors for LCDs. Anisotropic materials, such as quantum rods, have the additional advantage of polarized emission, which can bring a significant improvement to the efficiency of LCD displays. The basic optical properties of these nanomaterials are considered, with a focus on quantum rods, and the challenges and progress in their assembly are discussed. Different techniques for quantum rod alignment are introduced such as shear-oriented, electric field and magnetic field assisted assembly, mechanical rubbing, stretching, and electrospinning. The photoalignment approach allows for an easy arrangement of quantum rods in-plane, and the implications of this method to patterning are considered. Different configurations of LCDs utilizing semiconductor quantum dots and quantum rods as down-conversion layers are also presented, and the potential applications that are enabled by the wide range of emerging materials are highlighted.

18.
Nanoscale ; 11(43): 20837-20846, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31657423

RESUMO

Semiconductor quantum rods (QRs) show a polarized emission, which opens up the possibility of the enhancement of both brightness and color for liquid crystal displays (LCD) in the form of quantum rod enhancement films (QREFs) for LCD backlights. However, the QR alignment over a large area, suitable for displays, is a challenge. Inkjet printing of QREFs, introduced here, allows fabrication of well-aligned, uniform QREFs on photoaligned substrates using optimized QR inks. We observed that the ink composition and printing conditions affect the QR alignment quality significantly. A relative humidity of 50% with an exposure energy of 1 J cm-2 for the photoalignment process provided optimal conditions for QREFs. We have successfully shown a good QR alignment for 2.5-inch films and were able to align QRs in multiple layers. Thus, fabricated QREFs show a polarization ratio of 7.2 : 1 for the emitted light. These QREFs were combined with a blue LED and deployed as a backlight unit for an LCD which shows a brightness of ∼250 nits with an optical efficiency of ∼8%, reaching an NTSC of 109% in a CIE1976 color space. Thus, these printed QREFs, over a large area, provide an unprecedented increase of 77% in the optical efficiency of the LCDs and simultaneously offer better color performance.

19.
Adv Mater ; 29(33)2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28657203

RESUMO

Semiconductor nanorods (NR) emit polarized light, which is expected to bring manifold benefits, in terms of brightness and color enhancement, for modern liquid-crystal displays (LCD). In this regard, photoaligned nanorod enhancement films (NREF) for color and polarization conversion for LCD backlights are introduced here. The photoinduced anchoring forces, by the photoalignment layer, stimulate well-ordered self-assembly of NR in the thin polymer films. Green and red emitting NR with a quantum yield of ≈80% are aligned unidirectionally and in-plane, showing a polarization ratio of >7:1 and a degree of polarization of >0.81. The photoalignment technique facilitates the fabrication of mixed and multiple stacked NREF for LCDs, which improves the color gamut and polarization efficiency, and is thus expected to increase the optical efficiency of conventional LCDs by ≈60%.

20.
Lancet Oncol ; 18(6): 792-802, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28395880

RESUMO

BACKGROUND: Uveal melanoma is a rare tumour with no established treatments once metastases develop. Although a variety of immune-based therapies have shown efficacy in metastatic cutaneous melanoma, their use in ocular variants has been disappointing. Recently, adoptive T-cell therapy has shown salvage responses in multiple refractory solid tumours. Thus, we sought to determine if adoptive transfer of autologous tumour-infiltrating lymphocytes (TILs) could mediate regression of metastatic uveal melanoma. METHODS: In this ongoing single-centre, two-stage, phase 2, single-arm trial, patients (aged ≥16 years) with histologically confirmed metastatic ocular melanoma were enrolled. Key eligibility criteria were an Eastern Cooperative Oncology Group performance status of 0 or 1, progressive metastatic disease, and adequate haematological, renal, and hepatic function. Metastasectomies were done to procure tumour tissue to generate autologous TIL cultures, which then underwent large scale ex-vivo expansion. Patients were treated with lymphodepleting conditioning chemotherapy (intravenous cyclophosphamide [60 mg/kg] daily for 2 days followed by fludarabine [25 mg/m2] daily for 5 days, followed by a single intravenous infusion of autologous TILs and high-dose interleukin-2 [720 000 IU/kg] every 8 h). The primary endpoint was objective tumour response in evaluable patients per protocol using Response to Evaluation Criteria in Solid Tumors, version 1.0. An interim analysis of this trial is reported here. The trial is registered at ClinicalTrials.gov, number NCT01814046. FINDINGS: From the completed first stage and ongoing expansion stage of this trial, a total of 21 consecutive patients with metastatic uveal melanoma were enrolled between June 7, 2013, and Sept 9, 2016, and received TIL therapy. Seven (35%, 95% CI 16-59) of 20 evaluable patients had objective tumour regression. Among the responders, six patients achieved a partial response, two of which are ongoing and have not reached maximum response. One patient achieved complete response of numerous hepatic metastases, currently ongoing at 21 months post therapy. Three of the responders were refractory to previous immune checkpoint blockade. Common grade 3 or worse toxic effects were related to the lymphodepleting chemotherapy regimen and included lymphopenia, neutropenia, and thrombocytopenia (21 [100%] patients for each toxicity); anaemia (14 [67%] patients); and infection (six [29%] patients). There was one treatment-related death secondary to sepsis-induced multiorgan failure. INTERPRETATION: To our knowledge, this is the first report describing adoptive transfer of autologous TILs to mediate objective tumour regression in patients with metastatic uveal melanoma. These initial results challenge the belief that metastatic uveal melanoma is immunotherapy resistant and support the further investigation of immune-based therapies for this cancer. Refinement of this T-cell therapy is crucial to improve the frequency of clinical responses and the general applicability of this treatment modality. FUNDING: Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research.


Assuntos
Imunoterapia Adotiva , Linfócitos do Interstício Tumoral/transplante , Melanoma/terapia , Neoplasias Uveais/terapia , Adulto , Anemia/induzido quimicamente , Enucleação Ocular , Feminino , Subunidades alfa de Proteínas de Ligação ao GTP/genética , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/genética , Humanos , Infecções/induzido quimicamente , Linfopenia/induzido quimicamente , Masculino , Melanoma/genética , Melanoma/secundário , Metastasectomia , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Radioterapia , Critérios de Avaliação de Resposta em Tumores Sólidos , Trombocitopenia/induzido quimicamente , Condicionamento Pré-Transplante/efeitos adversos , Transplante Autólogo , Neoplasias Uveais/genética , Neoplasias Uveais/patologia
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