ADVANCED MATERIALS
·
2025
·
IF 26.8
Yinghao Ding,Xueying Zhu,Jian Wen,Junchao Xiong,Shengyi Zhang,Zhimou Yang,Zhi-Wen Hu
Antigen presentation deficiency restricted by class I major histocompatibility complex (MHC-I) causes low antigenicity and antigen escape in tumors, thereby limiting T-cell immunotherapy outcomes. Here, a combined tumor immunotherapy is developed, in which tumors can present exogenous non-tumor antigens, and adoptively transferred CD8 + T cells specific for these antigens are re-targeted to attack tumors. The approach leverages a cascade-responsive peptide self-assembly to co-deliver suitable antigens and the chemotherapeutic drug camptothecin (CPT) to tumors. As a proof-of-concept, to re-target ovalbumin (OVA)-specific OT-I CD8 + T cells against tumors, PSA (Nap-GFFpYE-ss-Ag) and CPSA (CPT-GFFpYE-ss-Ag) are constructed, containing an OVA-derived epitope OVA 257-264 and/or CPT. The design enables the release of a unique N-terminal extended OVA 257-264 and CPT into the cytosol. As a result, the extended antigen is efficiently presented on the tumor surface by MHC-I, and CPT further enhances this presentation. When combined with adoptively transferred OT-I CD8 + T cells, the approach effectively facilitates CD8 + T cell infiltration and tumor inhibition. Additionally, CPSA treatment sensitizes immune responses to programmed cell death-ligand 1 (PD-L1) blockade, allowing the approach to synergize with an anti-PD-L1 antibody for improved tumor eradication.
研究领域:
肿瘤免疫学
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纳米医学
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药物递送系统
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免疫治疗
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分子自组装
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产品关联
DOI
PubMed
高影响因子
Cell Death Discovery
·
2025
·Vol. 11
·期 1
·1-13
·
IF 7
Jiang Xiaoxiao,Fan Zhijin,Zhang Zhenzhen,Zeng Fanchu,Sun Tong,Li Yuchen,Huang Guojia,Nie Liming
Tumor cells balance ATP production and carbon skeleton synthesis by flexibly altering catabolic pathways to sustain their significant growth advantage. Uncouplers have shown potential for tumor suppression by converting chemical energy from catabolism into heat. However, their use may be limited due to indiscriminate metabolic interference in both tumor and normal cells, as well as the uncertainty surrounding their effects on the immune microenvironment. Herein, we found that low-dose uncoupler BAM15 promoted AMPK, AKT signaling, and the TCA cycle without increasing cell proliferation or inducing cell death in vitro, suggesting an increase in futile cycling. Intratumoral injection of 50 ng/mL BAM15 accelerated catabolic processes while inhibiting anabolic pathways, resulting in a metabolomic reshaping with increased levels of linoleic acid, C5DC, and others. These changes were shown to enhance tumor-killing effects by T cells. To reduce side effects on normal tissues and improve tumor retention, BAM15 was targeted for delivery by loading it into TCVs. This TCV-BAM15 treatment significantly increased CD8+ T cell counts and granzyme B levels. Our findings highlight a previously unrecognized therapeutic effect and signaling mechanism of low-dose BAM15 treatment in tumors. We propose that this novel strategy holds promise as a tumor immunity therapy with fewer adverse effects compared to free uncoupling drugs at high concentrations.
研究领域:
肿瘤学
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免疫学
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生物化学
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药理学
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产品关联
DOI
PubMed
高影响因子
NATURE CELL BIOLOGY
·
2025
·Vol. 27
·期 8
·1357-1366
·
IF 19.1
Du Xian,Li Wenyan,Li Guiying,Guo Chenyue,Tang Xuyi,Bao Rujuan,Li Runchang,Huang Haiyan,Xu Shuiyu,Yu Xiaoyan,Han Qiaoqiao,Wan Jie,Li Song,Sun Jiayuan,Zhao Ren,Ye Youqiong,Gao Qiang,Ni Zhi-Yu,Cui Xingang,Zou Qiang
Dietary nutrients are inextricably linked to antitumour immune responses. However, the effect of diet-derived galactose on antitumour immunity remains unclear. Here we show that dietary galactose augments CD8 + T cell immunity to suppress tumour progression. High-galactose feeding drives hepatocyte-derived insulin-like growth factor binding protein 1 (IGFBP-1) production, thus restraining IGF-1 signalling-dependent T cell exhaustion. IGF-1 receptor (IGF-1R) deficiency in T cells potentiates antitumour CD8 + T cell responses and phenocopies high-galactose feeding by preventing T cell exhaustion. Circulating galactose reprograms hepatocyte metabolism to inactivate mTORC1, thereby inducing the production of IGFBP-1 to boost CD8 + T cell function. Furthermore, patients with cancer who have high plasma IGFBP-1 levels exhibit blocked T cell exhaustion and enhanced T cell responses in tumour tissues. These findings reveal that dietary galactose specifically elicits potent antitumour CD8 + T cell responses by facilitating hepatocyte-derived IGFBP-1 production, providing insights into the development of more effective immunotherapies against cancers.
研究领域:
免疫学
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肿瘤学
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分子生物学
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转化医学
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代谢调控
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产品关联
DOI
PubMed
高影响因子
Nature Nanotechnology
·
2025
·
IF 34.9
Zhao Zhipeng,Li Qian,Qu Chenghao,Jiang Zeyu,Jia Guoqing,Lan Gongde,Luan Yuxia
Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of haematological malignancies. Challenges in overcoming physical barriers however greatly limit CAR-T cell efficacy in solid tumours. Here we show that an approach based on collagenase nanogel generally improves the outcome of T cell-based therapies, and specifically of CAR-T cell therapy. The nanogels are created by cross-linking collagenase and subsequently modifying them with a CXCR4 antagonist peptide. These nanogels can bind CAR-T cells via receptor–ligand interaction, resulting in cellular backpack delivery systems. The nanogel backpacks modulate tumoural infiltration and localization of CAR-T cells by surmounting physical barriers and disrupting chemokine-mediated CAR-T cell imprisonment, thereby addressing their navigation deficiency within solid tumours. Our approach offers a promising strategy for pancreatic cancer therapy and holds potential for advancing CAR-T cell therapy towards clinical applications.
研究领域:
肿瘤学
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免疫学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Targeted Oncology
·
2020
·Vol. 15
·期 3
·365-375
·
IF 4.036
Ding Shengnan,Mao Xia,Cao Yang,Wang Na,Xu Hao,Zhou Jianfeng
Background Although chimeric antigen receptor (CAR) T-cell therapy targeting antigens expressed in refractory and relapsed non-Hodgkin B-cell lymphoma, such as CD19 and CD22, has achieved encouraging clinical effects, some patients fail to attain remission, or relapse after CAR T-cell therapy, which has been ascribed to the loss of the target antigens. Objective To evaluate CD79b as an alternative target for CAR T-cell B-cell lymphoma therapy. Patient and methods The expression of CD79b in different B-cell lymphomas was determined. Anti-CD79b CAR T-cells expressing one of two different CARs were generated, and a series of in vitro and in vivo experiments were conducted to assess the CAR T-cell function. Results We found that CD79b was extensively expressed on the tumor cells of patients with various types of lymphoma regardless of stage, subtype, and cytogenetic and molecular features. Anti-CD79b CAR T-cells were highly specific and effective for the treatment of B-cell lymphomas. Conclusions Our data indicate that CD79b could be used as a target for CAR T-cell therapy of B-cell lymphomas, and further clinical development is warranted.
研究领域:
肿瘤学
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免疫学
·
血液学
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DOI
PubMed
高影响因子
Materials Today Bio
·
2023
·
IF 8.2
Yuxiang Tang,WeiQi Yao,Hang Hu,Wei Xiong,Heng Mei,Yu Hu
TGF-β is widely existed in tumor microenvironment, taking part in tumorigenesis process including angiogenesis, cancer associated fibroblast (CAF) proliferation, and immunosuppression. It inhibited the activation, proliferation, migration and differentiation of T cells, in which way caused a limited therapeutic effects of chimeric antigen receptor T (CAR-T) towards solid tumor such as lymphoma. To targeted block TGF-β at tumor site, we take advantages of nano-techniques to deliver TGF-β inhibitors LY2157299 (LY) towards the tumor sites, in order to help achieve a improved and long-term functions of CAR-T towards lymphoma. Based on amphipathic hydroxyethyl starch-polycaprolactone (HES-PCL), LY and photosensitizer indocyanine green (ICG) were co-loaded in HES-PCL to achieve LY/ [email protected] nanoparticle. The enhanced function of CAR-T benefited from LY/ [email protected] were verified through lymphoma Raji cells in vitro and Nod scid gamma mice engrafted with the Raji cells in vivo. LY was targeted transported to tumor site and accelerated release by mild ICG photothermal. Chemokines CXCL9/10/11 at the tumor site relevant to CAR-T migration and chemokines receptor CXCR3 of CAR-T could be up-regulated by LY, thus facilitated the enhanced accumulation of CAR-T at lymphoma site. T effector memory cells differentiation could also be accelerated by LY/ [email protected] Combined therapy of LY/ [email protected] and CAR-T achieved 2.4 times higher antitumor activity and 2.7 times higher relapse inhibiting rates than CAR-T alone within 15 days and 11 days, respectively. The results suggested that LY/ [email protected] facilitated the enhanced therapeutic index of CAR-T cells towards lymphoma simply and safely, it may be further potentiated applied for other solid tumors.
研究领域:
肿瘤学
·
免疫治疗
·
纳米技术
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2024
·
IF 5.8
Pan Li,Zihe Zhai,Jiawen Fang,Ruo Wang,Weiqi Li,Beiduo Wang,Jinglei Wang,Jiaqi Zhu,Feng Bing,Qiaoling Pan,ChangYou Gao,ShaoHong Lu
Together, tumor and virus-specific tissue-resident CD8+ memory T cells (TRMs) of hepatocellular carcinoma (HCC) patients with Hepatitis B virus (HBV) infection can provide rapid frontline immune surveillance. The quantity and activity of CD8+ TRMs were correlated with the relapse-free survival of patients with improved health. However, HBV-specific CD8+ TRMs have a more exhausted phenotype and respond more actively under anti-PDL1 or PD1 treatment of HBV+HCC patients. Vaccination strategies that induce a strong and sustained CD8+ TRMs response are quite promising. Herein, a biodegradable poly(D,L-lactide-co-glycolide) microsphere and nanosphere particle (PLGA N.M.P) delivery system co-assembled by anti-PD1 antibodies (aPD1) and loaded with ovalbumin (OVA-aPD1 N.M.P) was fabricated and characterized for size (200 nm and 1 μm diameter), charge (−15 mV), and loading efficiencies of OVA (238 μg mg−1 particles) and aPD1 (40 μg mg−1 particles). OVA-aPD1 N.M.P could stimulate the maturation of BMDCs and enhance the antigen uptake and presentation by 2-fold compared to free OVA. The nanoparticles also induced the activation of macrophages (RAW 264.7) to produce a high level of cytokines, including TNF-α, IL-6 and IL-10. In vivo stimulation of mice using OVA-aPD1 N.M.P robustly enhanced IFN-γ-producing-CD8+ T cell infiltration in tumor tissues and the secretion of IgG and IgG2a/IgG1 antibodies. OVA-aPD1 N.M.P delivered OVA to increase the activation and proliferation of OVA-specific CD8+ TRMs, and its combination with anti-PD1 antibodies promoted complete tumor rejection by the reversal of tumor-infiltrating CD8+ T cell exhaustion. Thus, PLGA N.M.P could induce a strong CD8+ TRMs response, further highlighting its therapeutic potential in enhancing an antitumor immune response.
研究领域:
癌症免疫学
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药学
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免疫治疗
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纳米技术
·
肿瘤生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2022
·Vol. 12
·期 1
·1-12
·
IF 4.996
Zhang Shangkun,Gu Chaojiang,Huang Lifang,Wu Han,Shi Jiangzhou,Zhang Zijian,Zhou Yong,Zhou Jingjiao,Gao Yang,Liu Jiaxing,Leng Yingqi,Liu Xiyu,Zhang Qinxing,Huang Liang,Tong Xiqin,Young Ken H.,Li Jiapeng,Zhu Haichuan,Zhang Tongcun
CAR T-cell therapy is well tolerated and effective in patients with Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). However, even second- generation anti-CD30 CAR T-cells with CD28 (28z) costimulatory domains failed to achieve the desired rate of complete responses. In the present study, we developed second-generation (CD28z) and third-generation (CD28BBz) CAR T-cells targeting CD30 and investigated their efficacy in vitro and in vivo. Both of CD28z and CD28BBz anti-CD30 CAR T cells were similar regarding amplification, T cell subsets distribution, T cell activity, effector/memory and exhaustion. However, we found that the 28BBz anti-CD30 CAR T-cells persist long-term, specifically homing to the tumor and mediating powerful antitumor activity in tumor xenograft models. Subsequently, we also demonstrated that the third generation anti-CD30 CAR T-cells have miner side effects or potential risks of tumorigenesis. Thus, anti-CD30 CAR T-cells represent a safe and effective treatment for Hodgkin lymphoma.
研究领域:
免疫疗法
·
肿瘤学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Foods
·
2024
·Vol. 13
·期 18
·2996
·
IF 4.7
Jing Wu,Huilin Li,Zhijuan Wang,Mingfei Pan,Shuo Wang
Tert-butylhydroquinone (TBHQ) is a phenolic substance that is commonly employed to prevent food oxidation. Excessive or improper utilization of this antioxidant can not only impact food quality but may also pose potential risks to human health. In this study, an ultrasensitive, stable, and easily operable ratiometric electrochemical sensor was successfully fabricated by combining the tubular (3,4-ethylenedioxythiophene) (T-PEDOT) with single-wall carbon nanohorns (SWCNHs) for the detection of TBHQ antioxidants in food. The SWCNHs/T-PEDOT nanocomposite fabricated through ultrasound-assisted and template approaches was employed as the modified substrate for the electrode interface. The synergistic effect of SWCNHs and T-PEDOT, which possess excellent electrical conductivity and catalytic properties, enabled the modified electrode to showcase remarkable electrocatalytic performance towards TBHQ, with the redox signal of methylene blue serving as an internal reference. Under optimized conditions, the SWCNHs/T-PEDOT-modified electrode demonstrated good linearity within the TBHQ concentration range of 0.01–200.0 μg mL−1, featuring a low limit of detection (LOD) of 0.005 μg mL−1. The proposed ratiometric electrochemical sensor displayed favorable reproducibility, stability, and anti-interference capacity, thereby offering a promising strategy for monitoring the levels of TBHQ in oil-rich food products.
研究领域:
食品科学
·
材料科学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2015
·Vol. 5
·期 43
·34451-34455
·
IF 3.84
Yu Liu,Weidong Chi,Hui Liu,Yueyang Su,Liang Zhao
Cubic and tetragonal ZrO2 were synthesized by a sol–gel method using ethanol and glycerol as solvents and ZrOCl2·8H2O as zirconium source. The effect of phase stabilization with amorphous carbon was observed and discussed. The structural evolution, phase transformation and morphological characteristics of powders were investigated by thermogravimetric analysis (TG), differential scanning calorimetric analysis (DSC), powder X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). Cubic and tetragonal phase could be generated in this system.
研究领域:
材料科学
·
陶瓷学
✓ 已验证
产品关联
DOI
高影响因子
DALTON TRANSACTIONS
·
2021
·Vol. 50
·期 41
·14532-14536
·
IF 4.39
Yang Zhang,Yakun Tang,Lang Liu,Yue Zhang,Zhiguo Li
A T-Nb2O5/CNT nanohybrid with short transmission paths, many active sites, and favorable mechanical flexibility can achieve the fast transportation of ions/electrons. The obtained nanohybrid with continuous conductive networks exhibited better lithium storage performance than sodium storage performance, due to lower resistance to the diffusion of Li+ ions crossing the carbon matrix.
研究领域:
材料科学
·
能源存储
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2021
·Vol. 11
·期 1
·1-9
·
IF 4.38
Yang Xin,Yu Qiuxia,Xu Hao,Zhou Jianfeng
Treatment failure or relapse due to tumor escape caused by reduction in target antigen expression has become a challenge in the field of CART therapy. Target antigen density is closely related to the effectiveness of CART therapy, and reduced or lost target antigen expression limits the efficacy of CART therapy and hinders the durability of CAR T cells. Epigenetic drugs can regulate histones for molecular modifications to regulate the transcriptional, translational and post-translational modification processes of target agents, and we demonstrated for the first time the role in regulating CD22 expression and its effect on the efficacy of CD22 CART. In this paper, we found that Chidamide promoted the expression of CD22 on the surface of B-cell tumor cells in vitro and in vivo, and enhanced the function of CD22 CART. As for mechanisms, we demonstrated that Chidamide did not affect CD22 mRNA transcription, but significantly increased the expression of total CD22 protein, indicating that Chidamide may upregulate cell surface CD22 expression by affecting the distribution of CD22 protein. In summary, our results suggest that Chidamide may enhance the efficacy of CD22 CART by inhibiting histone deacetylases to regulate post-transcriptional modifications that affect protein distribution to increase the expression of CD22 on the cell surface.
研究领域:
肿瘤学
·
免疫疗法
·
分子生物学
·
表观遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）