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The directed self-assembly strategy endows the ultrasmall metal nanocluster (MNC, <3 nm) superstructure assemblies with enhancement of inherent characteristics or generation of novel properties, which has aroused great interests in multidisciplinary applications, including catalysis, bioimaging, and optics. However, the precise synthesis of ultrastable hydrophilic MNC assemblies remains a challenge. Herein, rationally designed star-like polymer unimolecular micelles were used as scaffold nanoreactors for the precise in situ confined synthesis of hydrophilic spherical MNC superstructure assemblies (Au, Ag, Cu, Pt, and AuAg alloy) in aqueous solution. By effectively proceeding with photoinduced atom transfer radical polymerization (photoATRP), the size of the MNC assembly could be precisely customized. The thiolate ligands were utilized to control the ultrasmall size of single MNCs and greatly improve the catalytic stability via the bridging interaction with the polymer template. Moreover, deep red to NIR emitting photoluminescent MNC assemblies could be realized via adjusting the aggregation-induced emission properties of the Au(I)-SR complex motif and the molecular weight of the polymer template. Thus, we anticipate that this strategy may contribute a practical solution to broadly create hydrophilic ultrastable well-defined MNC assemblies with many unforeseen properties in a precise way for applications in catalysis, optics, and biology fields.

The exploration of pharmaceutically active agents and positron emission tomography (PET) tracers targeting CXCR4 has been a focal point in cancer research given its pivotal role in the development and progression of various cancers. While significant strides have been made in PET imaging with radiometal-labeled tracers, the landscape of 18F-labeled small molecule tracers remains relatively limited. Herein, we introduce a novel and promising derivative, [18F]SFB-AMD3465, as a targeted PET tracer for CXCR4. The compound was synthesized by modifying the pyridine ring of AMD3465, which was subsequently labeled with 18F using [18F]SFB. The study provides comprehensive insights into the design, synthesis, and biological evaluation of [18F]SFB-AMD3465. In vitroand in vivoassessments demonstrated the CXCR4-dependent, specific, and sensitive uptake of [18F]SFB-AMD3465 in the CXCR4-overexpressing 4T1 cell line and the corresponding xenograft-bearing mouse model. These findings contribute to bridging the gap in 18F-labeled PET tracers for CXCR4 and underscore the potential of [18F]SFB-AMD3465 as a PET radiotracer for in vivoCXCR4 imaging.

Multiple myeloma (MM), a hematological malignancy of plasma cells, has remained largely incurable owing to drug resistance and disease relapse, which requires novel therapeutic targets and treatment approaches. Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) acts as an oncoprotein linked to the development of various tumors. However, the functional consequence of Pin1 overexpression in modulating MM biology has not been established. In the present study, we show that Pin1 expression is highly variable in myeloma cell lines and primary MMs and that high Pin1 expression is associated with poor survival of MM patients. Next, TOP2A is identified to be a Pin1 promoter-binding protein and CK2 activates TOP2A to promote the expression level of Pin1. Additionally, we demonstrate that Pin1 positively modulates the stability and function of Pyk2 to enhance bortezomib resistance in MM. Pin1 recognizes three phosphorylated Ser/Thr-Pro motifs in Pyk2 via its WW domain and increases the cellular levels of Pyk2 in an isomerase activity-dependent manner by inhibiting the ubiquitination and proteasomal degradation of Pyk2. Moreover, Pin1 inhibition combined with Pyk2 inhibition decreases myeloma burden both in vitro and in vivo. Altogether, our findings reveal the tumor-promoting role of Pin1 in MM and provide evidence that targeting Pin1 could be a therapeutic strategy for MM.

Epidermal growth factor receptor pathway substrate number 8 (EPS8) has been reported to be critical in mediating tumor progression. However, the molecular and biological consequences of EPS8 overexpression remain unclear. Here we evaluated whether EPS8 increased DNA damage repair in non-small-cell lung carcinoma (NSCLC) cells and the mechanism of EPS8-mediated DNA damage repair which influenced chemosensitivity. Serial studies of functional experiments revealed that EPS8 knockdown inhibited cell growth, induced cell-cycle arrest and increased cisplatin therapeutic effects on NSCLC. EPS8 was found to induce DNA damage repair via upregulation of phosphorylated-ATM and downregulation of the tumor suppressor p53 and G1 cell kinase inhibitor p21. Moreover, in conjunction with cisplatin, decreasing EPS8 protein levels further increased p53 protein level and inhibited ATM signaling. Transplanted tumor studies were also performed to demonstrate that EPS8 knockdown inhibited tumor growth and sensitized tumors to cisplatin treatment. In conclusion, we have described a novel molecular mechanism through which EPS8 is likely to be involved in cancer progression and chemoresistance via DNA damage repair, indicating that EPS8 expression may influence the response to chemotherapy. Therefore, targeting EPS8 may be a potential therapeutic approach for patients with NSCLC.

Near-infrared (NIR) light-mediated polymerization has been of particular interest owing to the deep penetration into opaque materials, giving rise to great potential for biomedical applications and solar photochemistry. Photoinduced electron/energy transfer-reversible addition–fragmentation chain transfer (PET-RAFT) polymerization presented unprecedented spatiotemporal control over the controlled radical polymerization process. Herein, we greatly extended the NIR region up to 980 nm by introducing rationally designed upconversion nanocrystals with low toxicity and resistance to photobleaching into PET-RAFT polymerization. Well-defined polymers with predictable molecular weight and narrow dispersity were prepared within a few hours by 980 nm NIR light-regulated PET-RAFT polymerization via the energy transfer upconversion mechanism. The livingness feature of this photopolymerization was confirmed by polymerization kinetics, chain extension experiments, and multiple controlled “on–off” light switching cycles. Furthermore, the polymerizations could be successfully performed using different monomers, in the presence of several visible light-proof barriers (i.e., pork/chicken skin) and even under aerobic conditions, demonstrating the multifold advantages of our approach.

Photoinduced atom transfer radical polymerization (ATRP) has been proved to be a versatile technique for polymer network formation. However, the slow polymerization rates of typical ATRP limited its application in the field of additive manufacturing (3D printing). In this work, we introduced carbon quantum dots (CQDs) for the first time to the ATRP in aqueous media and developed an ultrafast visible-light-induced polymerization system. After optimization, the polymerization could achieve a high monomer conversion (>90%) within 1 min, and the polydispersity index (PDI) of the polymer was lower than 1.25. This system was then applied as the first example of ATRP for the 3D printing of hydrogel through digital light processing (DLP), and the printed object exhibited good dimensional accuracy. Additionally, the excellent and stable optical properties of CQDs also provided interesting photoluminescence capabilities to the printed objects. We deduce this ATRP mediated 3D printing process would provide a new platform for the preparation of functional and stimuli-responsive hydrogel materials.

Trivalent arsenic (AsIII) is an effective agent for treating patients with acute promyelocytic leukaemia, but its ionic nature leads to several major limitations like low effective concentrations in leukaemia cells and substantial off-target cytotoxicity, which limits its general application to other types of leukaemia. Here, building from our clinical discovery that cancerous cells from patients with different leukaemia forms featured stable and strong expression of CD71, we designed a ferritin-based As nanomedicine, As@Fn, that bound to leukaemia cells with very high affinity, and efficiently delivered cytotoxic AsIIIinto a large diversity of leukaemia cell lines and patient cells. Moreover, As@Fn exerted strong anti-leukaemia effects in diverse cell-line-derived xenograft models, as well as in a patient-derived xenograft model, in which it consistently outperformed the gold standard, showing its potential as a precision treatment for a variety of leukaemias.

Despite recent progress in synthesis, self-assembly, and utility of low band gap lead chalcogenide nanoparticles (NPs) due to their intriguing optoelectronic characteristics, their compositional instability in ambient condition remains a great challenge for long-term practical applications. Herein, we report a unique strategy via capitalization on a set of starlike block copolymers as nanoreactors for in situ crafting of uniform lead chalcogenide NPs with readily tailored sizes, surface chemistry, near-infrared (NIR) optoelectronic properties, and more importantly, markedly enhanced stability against air exposure. The intimate and permanent tethering of the outer blocks of starlike block copolymers on the surface of lead chalcogenide NPs imparts their effective dispersion in both the solution and dry state. The diameter of the resulting NPs can be conveniently tuned by regulating the molecular weight (i.e., length) of the inner hydrophilic blocks of starlike block copolymers, manifesting the progressive red shift in the NIR absorption and emission as the diameter of the NPs increases. Most intriguingly, judiciously alternating the compositions and chain lengths of the outer blocks of the starlike block copolymers renders remarkably improved stability of lead chalcogenide NPs in ambient condition, representing no spectral change in both position and intensity for 30 days as compared to rapid and complete quenching of emission in 1 day in conventional small-molecular-ligand-capped counterparts. In principle, our starlike block copolymer nanoreactor strategy can be easily extended to synthesize functional NPs other than metal chalcogenides for investigation into their dimension-dependent physical properties and self-assembly as well as various applications.

A series of amphiphilic star-like triblock copolymers with well-defined molecular architectures, molecular weight, and narrow polydispersity were successfully synthesized by sequential atom transfer radical polymerization (ATRP) using β-cyclodextrin as the initiator. These star-like triblock copolymers are composed of poly(4-vinyl pyridine) (P4VP) as the first block, poly(tert-butyl acrylate) (PtBA) as the second block, and either polystyrene (PS), poly(methyl methacrylate) (PMMA), or poly(ethylene oxide) (PEO) as the third block (denoted as P4VP-b-PtBA-b-PS, P4VP-b-PtBA-b-PMMA, and P4VP-b-PtBA-b-PEO, respectively). Notably, by deliberate addition of a linear initiator [i.e., ethyl α-bromoisobutyrate (EBiB)] into the polymerization reaction when growing the second PtBA block (i.e., synthesis of star-like P4VP-block-PtBA; denoted as P4VP-b-PtBA), a suitable concentration of Cu2+can be achieved. This suppresses further termination reactions between active chain ends of star-like polymer, thus rendering the ability to better control the growth of star-like P4VP-b-PtBA diblock copolymer (polydispersity index; PDI < 1.2). Kinetic studies of PtBA polymerization with and without the addition of linear initiators of EBiB were conducted. Importantly, the living nature of ATRP of star-like P4VP-b-PtBA diblock copolymer can only be attained when the linear initiator was added. Subsequently, star-like P4VP-b-PtBA-b-PS, P4VP-b-PtBA-b-PMMA, and P4VP-b-PtBA-b-PEO were synthesized by using star-like P4VP-b-PtBA as the macroinitiator via ATRP (for hydrophobic PS and PMMA) and click reaction (for hydrophilic PEO), respectively, further confirming the tunability of surface chemistry (i.e., the outer block of star-like triblock copolymers) in this system. Finally, after hydrolyzing PtBA into poly(acrylic acid) (PAA), the dual pH-responsive behaviors of double hydrophilic star-like P4VP-b-PAA diblock copolymer were explored. In addition to dual pH-responsiveness, the strategy we developed based on sequential ATRP via cyclodextrin as the initiator in this study may conveniently enable the synthesis of a rich variety of other stimuli-responsive unimolecular star-like block copolymers comprising dissimilar blocks that are either pH-responsive, thermo-responsive, or photo-responsive. As such, they may afford a unique platform for fundamental research and applications in smart delivery vehicles, sensors, and tunable templates for nanomaterials.

Introduction:

We report a simple, robust, and inexpensive strategy to enable all-inorganic CsPbX3perovskite nanocrystals (NCs) with a set of markedly improved stabilities, that is, water stability, compositional stability, phase stability, and phase segregation stability via impregnating them in solid organic salt matrices (i.e., metal stearate; MSt). In addition to acting as matrices, MSt also functions as the ligand bound to the surface of CsPbX3NCs, thereby eliminating the potential damage of NCs commonly encountered during purification as in copious past work. Quite intriguingly, the resulting CsPbX3–MSt nanocomposites display an outstanding suite of stabilities. First, they retain high emission in the presence of water because of the insolubility of MSt in water, signifying their excellent water stability. Second, anion exchange between CsPbBr3–MSt and CsPbI3–MSt nanocomposites is greatly suppressed. This can be ascribed to the efficient coating of MSt, thus effectively isolating the contact between CsPbBr3and CsPbI3NCs, reflecting notable compositional stability. Third, remarkably, after being impregnated by MSt, the resulting CsPbI3–MSt nanocomposites sustain the cubic phase of CsPbI3and high emission, manifesting the strikingly improved phase stability. Finally, phase segregation of CsPbBr1.5I1.5NCs is arrested via the MSt encapsulation (i.e., no formation of the respective CsPbBr3and CsPbI3), thus rendering pure and stable photoluminescence (i.e., demonstration of phase segregation stability). Notably, when assembled into typical white light-emitting diode architecture, CsPbBr1.5I1.5–MSt nanocomposites exhibit appealing performance, including a high color rendering index (Ra) and a low color temperature (Tc). As such, the judicious encapsulation of perovskite NCs into organic salts represents a facile and robust strategy for creating high-quality solid-state luminophores for use in optoelectronic devices.

Chemical inertness of BNNS seriously restricts its application for fabricating thermally conductive polymer-based composites with uniform dispersion and low interfacial thermal resistance. In this work, by using self-initiated photografting and photopolymerization (SIPGP) method, over 40 wt% polyacrylic acid (PAA) macromolecular chains can be grafted onto BNNS in only 2 h for improving polarity and water dispersibility of BNNS, and the content of grafted PAA can be easily tuned by the reaction time. Furthermore, based on the coordination effect between carboxyl groups of PAA and Au3+/AuNPs, large amount of AuNPs can be immobilized onto BNNS to form hetero-structured AuNPs@BNNS hybrid filler, and such filler is beneficial for decreasing interfacial thermal resistance between fillers, constructing thermally conductive network in relatively lower filler content and improving comprehensive thermal conductivity. Finally, AuNPs@BNNS/NFC composite with only 30 wt% filler can reach in-plane and through-plane thermal conductivities of 19 and 1.22 W/(m·K) simultaneously. Therefore, this study provides a simple and effective method to fabricate water-dispersible and hetero-structured AuNPs@BNNS hybrid filler, which can be used for preparation of high-efficiency thermal management materials for electronic devices effectively.

The ability to create a synergistic effect of nanostructure engineering and its hybridization with conductive carbonaceous material is highly desirable for attaining high-performance lithium ion batteries (LIBs). Herein, we judiciously crafted ZnFe2O4/carbon nanocomposites composed of ZnFe2O4nanoparticles with an average size of 16 ± 5 nm encapsulated within the continuous carbon network as anode materials for LIBs. Such intriguing nanocomposites were yielded in situ viathe pyrolysis-induced carbonization of polystyrene@poly(acrylic acid) (PS@PAA) core@shell nanospheres in conjunction with the formation of ZnFe2O4nanoparticles through the thermal decomposition of ZnFe2O4precursors incorporated within the PS@PAA nanospheres. By systematically varying the ZnFe2O4content in the ZnFe2O4/carbon nanocomposites, the nanocomposite containing 79.3 wt % ZnFe2O4was found to exhibit an excellent rate performance with high capacities of 1238, 1198, 1136, 1052, 926, and 521 mAh g–1at specific currents of 100, 200, 500, 1000, 2000, and 5000 mA g–1, respectively. Moreover, cycling performance of the ZnFe2O4/carbon nanocomposite with 79.3 wt % ZnFe2O4at specific currents of 200 mA g–1delivered an outstanding prolonged cycling stability for several hundred cycles.

A novel mixed powders made up of laboratory-made thermoplastic polyether-block-amide (TPAE) and multiwalled carbon nanotubes (MWCNTs) for the selective laser sintering (SLS) 3D printing have been prepared through an environment-friendly approach and the carbon nanotube conductive network structure is established in the SLS-processed nanocomposite devices. The electrical properties, strain sensing property and electro-induced shape memory effect of flexible TPAE/MWCNTs nanocomposites are fully investigated. The conductivity of TPAE/MWCNTs nanocomposites increases as the MWCNTs content increases owing to the interconnected MWCNTs conductive network. During compressing test with different deformation strain and speed, the SLS-processed flexible sensor exhibits a regular, fast, sensitive and stable cyclic response which shows its great potential for artificial electronic skin, human-machine interface and health monitoring. The TPAE-5.0C nanocomposite also possessed an excellent shape recovery ability during electro-induced shape memory cycle which was triggered by Joule heat under DC voltage. The MWCNTs-TPAE powder prepared here provides a novel material for SLS 3D-printing and the SLS-processed devices with outstanding performance and multiple functions will be very useful for developing flexible and lightweight wearables in the future.

Excellent thermal management property and high-temperature dimensional stability are very important for the materials applied in the electronic devices. In this study, high temperature resistant PA12T was applied as the matrix, and PA12T/BN composites with oriented structure were fabricated by the injection molding method. Morphology, thermal conductivity, thermal expansion property and mechanical properties of the composite were systematically investigated. Results demonstrate that when the content of BN is 40 wt%, the in-plane thermal conductivity and thermal expansion coefficient of the composites are 6.5 W/(m·K) and 36 ppm/°C, respectively, which are 4 times higher and 80% lower than those along the through-plane direction. Meanwhile, the thermal expansion behavior and mechanism of the composite with oriented filler structure are well revealed by finite element analysis, and the simulated results will provide important guidance for the design and application of the composite. Furthermore, by using the PA12T/BN composite with oriented structure as the substrate of printed circuit board, temperature gradient as well as thermal stress inside the device can be well controlled. Therefore, the PA12T/BN composite has great potential in the application as the substrate or packaging materials of electronic devices.

Although composite magnetic materials based on iron oxide or ferric oxide have attracted much attention in both basic research and practical applications, the strong visible light absorption always limited their applications as optical or luminescent materials. Here we prepared paramagnetic photoluminescence composite colloidal polymer nanoparticles of P(PEGA)-b-P(AA-co-TPEE) by introducing holmium (Ho) to the assembly. The high magnetic moment of Ho endow paramagnetic behavior to the P(PEGA)-b-P(AA-co-TPEE)/Ho composite particles, and the saturation magnetization value of the P(PEGA)-b-P(AA-co-TPEE)/Ho increased with the increase content of Ho. Owing to the low chroma, Ho has little effect on the light absorption of polymer matrix and would not affect the photoluminescence (PL) behavior of TPEE block in the polymer chains. The coordination of Ho3+and carboxyl groups decreased the hydrophilicity of PAA blocks, and induced the formation of composite colloidal nanoparticles with different morphologies. Therefore, the relationship between the PL intensity, Ho3+concentration and saturation magnetization value of the composites could be built. In addition to be paramagnetic photoluminescence composite material, the P(PEGA)-b-P(AA-co-TPEE)/Ho composite particle can be used as a multifunctional carrier for fixed-point release under magnetic field, and can also be used for fluorescence imaging.

Human promyeloblastic leukemia KG-1a cells exhibit many characteristics similar to leukemia stem cells, which are resistant to chemotherapeutic drugs and hyposensitive to cytotoxic cells. Resveratrol (RES), as a member of plant polyphenols, has gained considerable attention due to its ability to prevent cancer from progressing. In this study, the potential of RES to sensitize KG-1a cells to cytolysis of cytokine-induced killer cells (CIKs) through NKG2D ligands and TNF-related apoptosis-inducing ligand (TRAIL) receptors were investigated. Twenty-five micromolars RES was found to inhibit approximately 50% of KG-1a cell growth and had the least growth-inhibition effect on peripheral blood mononuclear cells (PBMCs) after 24 h. Utilizing cytokines including interleukin-2 (IL-2) and interleukin-15 (IL-15) to activate PBMCs, we obtained substantial CD3+CD56+natural killer cell-like T lymphocytes that secreted cytokine interferon-γ (IFN-γ) and expressed NKG2D and TRAIL on their surfaces (i.e., cytokine-induced killer cells, CIKs). RES was shown to render KG-1a cells susceptible to CIK-mediated cytolysis estimated by LDH-release assay. This heightened sensitivity correlated with an increase in cell-surface expression of NKG2D ligands and death receptor 4 (DR4), coupled with a downregulation of cell-surface expression of decoy receptor 1 (DcR1) in KG-1a cells. Blocking NKG2D ligands or TRAIL with monoclonal antibodies could abrogate CIKs-mediated cytolysis. These results demonstrated that increased sensitivity of KG-1a cells, modulated by RES to alloreactive CIKs-mediated cytolysis is a phenomenon attributable to induced expression of NKG2D ligands and activation of TRAIL pathway. Thus, resveratrol combined with alloreactive CIKs merits clinical evaluation as a novel and effective immunotherapy strategy to eliminate residual leukemia stem cells.

The utilizing light with broadband range has attracted lots of research interest for the photo induced reversible-deactivation radical polymerization (RDRP). However, it is still a challenge for a single catalyst to simultaneously respond to various lights with highly varied wavelengths. Here, we proposed a simple strategy for the preparation of a heterogeneous photocatalyst suitable for photo induced atom transfer radical polymerization (photoATRP) under full spectrum (from UV/vis light to NIR), by combining pyridine nitrogen doped carbon dots (N-CDs) and upconversion nanoparticles (UCNPs). In the presence of these robust UCNP@SiO2@N-CDs composite particles, the photoATRP could be carried on under the different irradiations of UV, blue, green, red, white, and 980 nm NIR light, with a low loading of part per million concentrations of the CuBr2/L catalyst. Moreover, the excellent solvent and aqueous compatibility allow UCNP@SiO2@N-CDs to be capable for photoATRP in both organic solvents and aqueous media, providing well-defined hydrophobic and hydrophilic polymers with low dispersity and excellent chain-end fidelity. In addition, the photoATRP with 980 nm NIR exhibited excellent penetrations through visible-light-proof barriers. The system could be used for the preparation of an injectable hydrogel that had dual curing and photoluminescence modes. Owing to the “living” characteristics of polymer chains achieved through ATRP, the hydrogel was capable to be easily repaired by using monomer as the binder.

Ultrasmall noble metal nanoclusters (NCs; core size, <2 nm) with a high surface atomic ratio and a tunable electronic structure have attracted intensive interest; however, the controlled preparation of stable metal NC assemblies is still a challenge. Here, star-like diblock copolymer unimolecular micelles were used as a universal and robust scaffold to synthesize ultrasmall metal NC assemblies with a controlled size and amount of metal NCs (10–160). The size of the NC assemblies can also be controlled by changing the length of the P4VP block of the star-like polymers via atom transfer radical polymerization. The thiolate ligands play an important role in the control of the size of individual nanoclusters and largely enhance the stability of the NC assemblies. The as-synthesized stable ultrasmall metal NC assemblies will have broad application prospects in the fields of catalysis, optics, and biomedicine.

A colloidal nanocrystal cluster (CNC) is a hierarchical nanostructure formed by clustering several nanocrystals into one nano-ensemble, which may exhibit unique optical or catalytic properties different from individual nanocrystals owing to the mutual interactions among neighboring component nanocrystals. However, there is still no universal synthetic route that could be applicable to diverse material compositions with precisely controlled hierarchical structures (i.e., nanocrystal number density, component nanocrystal size, and overall diameter of the CNC) up to now. Herein, a general and novel synthetic strategy was reported for crafting a wide range of inorganic CNCs (i.e., noble metal, semiconductor, and metal oxide) via utilizing amphiphilic star-like poly(4-vinylpyridine)-block-polystyrene diblock copolymers as nanoreactors prepared by sequential atom transfer radical polymerization. The hierarchical structure of rationally designed CNCs could be readily tailored by varying the P4VP molecular weight of star-like nanoreactors and the parameter optimization during the CNC preparation process, which was inaccessible by conventional synthetic methods.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

Background:Chimeric antigen receptor-modified T cells (CARTs) targeting CD19 has illustrated therapeutic efficacy in diffuse large B cell lymphoma (DLBCL). However, severe cytokine release syndrome (sCRS) reaction and CAR-T-cell-related encephalopathy syndrome (CRES) are the main adverse reactions of CART therapy. Because of the concern of severe CRES which is associated with potential mortality, patients with primary central nervous system Lymphoma(PCNSL) are excluded in most of CART clinical trials. CD70 is a promising therapeutic target due to the restricted expression pattern in normal tissues and overexpression in some lymphoma tissues, so CD70 specific CARTs maybe avoid CD19-negative relapse .Here we report a case with refractory and relapsed PCNSL who achieved long-term disease-free survival by combination therapy of CD19 and CD70 specific CARTs without inducing CRS or CRES.

Background:CD19 targeting chimeric antigen receptor T cells(CART19) therapy have shown great therapeutic potential in relapsed and refractory B cell acute lymphoblastic leukemia (ALL), but associated with risk of life-threatening adverse effects as severe cytokine release syndrome (sCRS) and CAR-T-cell-related encephalopathy syndrome (CRES).It's been reported that high leukemia burden before CART therapy, and high does infused CART cells are associated with severity of CRS and CRES. To decrease the risk of severe adverse effect, we applied integrated therapeutic strategy of using fourth generation CART cells , reducing leukemia blasts burden in bone marrow, and decreasing the dose of infused CART cells (www.clinicaltrials.gov; #NCT03407859 and #NCT03125577 ).

No relevant conflicts of interest to declare.

Abstract 4738

No relevant conflicts of interest to declare.