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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

Donor-receptor coordination mediated multiple antigens capture and transport for augmented cancer immunotherapy

Huan Liang,Qingqing Lu,Runyu Hu,Yixiao Zhang,Xing Rong,Guocan Yu,Jie Yang

The activation of tumor antigen-specific immune responses is critical for the success of tumor immunotherapy and the advancement of antitumor therapies. However, the limited availability of antigens derived from immunogenic cell death significantly impedes antitumor immunity. To optimize the utilization of the resulting antigens and enhance the tumor-specific immune response, we herein present a strategy that captures antigens in situ within a polymeric depot, facilitated by donor-receptor coordination interactions. An amphiphilic cationic copolymer containing pendant phenylboronic acid (PP) as an electron acceptor unit was synthesized to facilitate various forces with multiple antigens, thereby generating nanovaccines in situ. As the most potent antigen are cell membrane, phenylboronic acid can specifically interact with sialylated epitopes overexpressed on the tumor cell membrane through the formation of donor-receptor coordination. For antigen proteins, the PP could bind with antigens by hydrophobic or electrostatic interaction, thereby facilitating their capture and delivery into the cytosol of antigen-presenting cells (APCs) and activating tumor-specific T cells. This platform could be adapted for various antigens, including antigen protein, tumor lysate and tumor cell membrane, with electron-donating groups, providing a straightforward and robust strategy to enable nanovaccines with enhanced antigen capture capabilities, ultimately improving cancer immunotherapy.

CAS / MDL: 65-85-0
研究领域: 免疫学 · 纳米技术 · 肿瘤学 · 生物化学 · 药学
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ANALYTICAL BIOCHEMISTRY · 2018 · IF 2.275

Trypsin enhances aptamer screening: A novel method for targeting proteins

Lide Gu,Wanli Yan,Shu Liu,Wei Ren,Mingsheng Lyu,Shujun Wang

A novel screening method for protein aptamer selection was developed in this study. Aptamers with high affinity and specificity to the surface recombinant antigen of Helicobacter pylori (HP-Ag) and to tumor markers carcinoembryonic antigen (CEA), cancer antigen 125 (CA125) and cancer antigen 19-9(CA19-9) were screened using trypsin enhanced screening method. Briefly, the target proteins above were immobilized onto 96-well polystyrene plates and incubated with a single-stranded DNA (ssDNA) library for aptamer selection. Then, trypsin was introduced to digest the proteins and obtain ssDNA that bound to the target proteins with high specificity. The concentration of ssDNA that shed from protein-ssDNA complexes was detected. After sequencing, the enrichment of target-specific aptamers was monitored and the affinity of each aptamer was analyzed. Urea, which has been reported in other article, was used to compare with trypsin. The results revealed that trypsin was more effective than urea for protein aptamer selection. The protocol used in this study provided a novel method for generating aptamers.

CAS / MDL: 79-06-1 57-13-6
研究领域: 分子生物学 · 生物技术 · 蛋白质工程
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Targeted Oncology · 2020 ·Vol. 15 ·期 3 ·365-375 · IF 4.036

Targeting CD79b for Chimeric Antigen Receptor T-Cell Therapy of B-Cell Lymphomas

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 · 免疫学 · 血液学
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Oncotarget · 2017 · IF 5.168

Application of a double-colour upconversion nanofluorescent probe for targeted imaging of mantle cell lymphoma

Guang Yang,Yong Cao,Bin Yan,Qiang Lv,Jianbo Yu,Fusheng Zhao,Zhihong Chen,Heran Yang,Mengxi Chen,Zaishun Jin

Upconversion nanoparticles are a new type of fluorescent marker in biomedical imaging that can convert a longer wavelength (such as near-infrared fluorescence) into a shorter wavelength (such as visible light). Mantle cell lymphoma, which is derived from B-cell lymphoma, is a subtype of non-Hodgkin's lymphoma, and the immune phenotype is a mature B-cell phenotype (CD20+, CD5+). To develop the use of nanomaterials as specific markers for the medical imaging of mantle cell lymphoma, we modified the surface of UCNPs by oxidation so that the CD20 or CD5 antibody could covalently attach to the upconversion nanoparticles to form antibody-UCNP conjugates. These antibody-UCNP conjugates were used as fluorescent probes to detect the CD20 or CD5 antigen. Due to the excessive expression of these antigens on the surface of MCL cells and successful strong connection between the antibody and UCNPs, the latter could specifically combine with mantle cell lymphoma cells. Upon near-infrared excitation at 980 nm, cells labelled with UCNPs emitted bright upconversion fluorescence.

研究领域: 生物医学工程 · 肿瘤学 · 纳米医学
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ANALYTICAL CHEMISTRY · 2025 · IF 6.7

A Label-Free Method Combining Chromatography Enrichment with N-Terminal Specific Proteolysis Enables Sensitive Identification of Tn/sTn Glycosites

Zhongyu Wang,Yan Wang,Taiheng Ma,He Zhu,Deguang Sun,Zhimou Guo,Xinmiao Liang,Mingliang Ye,Mingming Dong

Tn (GalNAcα1-O-S/T) and sTn (Neu5Acα2-6GalNAcα1-O-S/T) antigens, the immature O-glycans, are strongly correlated with cancer aggressiveness. Tn and sTn antigens exhibit significant differences between patients and healthy people, and they have emerged as potential biomarkers for cancer diagnosis and prognosis. Even though several chemical or chemoenzymatic labeling methods have been developed, the simultaneous analysis of Tn and sTn glycosites at the proteome level still faces great challenges. Here, we propose a label-free method for the sensitive identification of Tn/sTn glycosites from complex proteome samples. Because Tn/sTn antigens often densely occur on protein regions rich in Ser/Thr residues but lacking Lys/Arg residues, the trypsin digestion of these O-glycoproteins will generate relatively large peptides carrying multiple O-glycans. In this study, large tryptic O-glycopeptides were specifically enriched using hydrophilic interaction liquid chromatography. Subsequently, glycopeptides containing a single Tn/sTn antigen were generated by N-terminal-specific protease digestion, enabling the identification of Tn/sTn glycosites at the peptide N-termini. We demonstrated the general applicability of this method to analyze challenging samples, including HeLa cells and pancreatic ductal adenocarcinoma serum, where Tn/sTn are low-abundance O-glycans. Furthermore, a total of 191 Tn/sTn glycosites were identified on 200 glycopeptides from 136 proteins across two pancreatic cancer cell lines and serum. In summary, the method is broadly applicable, sensitive and well fitted to analyze a large cohort of clinical samples.

CAS / MDL: 69227-93-6
研究领域: 生物化学 · 分子生物学 · 肿瘤学 · 蛋白质组学
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ANALYTICAL BIOCHEMISTRY · 2020 · IF 2.877

Quick and convenient construction of lambda-cyhalothrin antigen for the generation of specific antibody

Nan Cui,Limin Cao,Jianxin Sui,Hong Lin,Xiangning Han,Xiangfeng Chen,Hanyi Xie,Xun Sun

Lambda-cyhalothrin is a pyrethroid widely used in crop, fruit and vegetable production, but has potential health threats to human. Immunoassay is a cheap, rapid and facile method to detect lambda-cyhalothrin, yet wide application of this method still requires improvement in the construction of antigen. In this study, we developed a one-step lambda-cyhalothrin hapten synthesis that transformed the cyanide group in lambda-cyhalothrin to amide. Complete antigen was assembled by coupling the amide with succinic-anhydride-activated carrier proteins, and corresponding polyclonal antibodies were generated using Balb/c mice. Using antibody generated by the method in this paper, the competitive ELISA demonstrated the lowest detection limit of 3.772 μg/L for lambda-cyhalothrin, and no significant cross-reactivity for other pyrethroid pesticides was observed. All the results suggested we have established a more efficient technique of generating lambda-cyhalothrin antibody. Furthermore, since the activated proteins used in this study are highly controllable, we believe these proteins could potentially be the prototype of a series of standardized carrier proteins for the synthesis of complete antigens.

CAS / MDL: 7631-86-9
研究领域: 农业化学 · 分析化学 · 毒理学
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2019 · IF 3.571

Characterization of a Histo-Blood Group Antigen-like Substance in Romaine Lettuce That Contributes to Human Norovirus Attachment

Zilei Zhang,Danlei Liu,Qingping Wu,Yu Lu,Peng Tian,Zhongfu Wang,Dapeng Wang

Human noroviruses (HuNoVs) are among the main pathogens causing acute nonbacterial gastroenteritis. Histo-blood group antigens (HBGAs) are widely accepted receptors for HuNoV specific binding. HBGA-like substances in produce are also considered as the critical ligands for capture of HuNoVs. However, the composition of viral ligands from food substrates remains unknown. In this study, an oligosaccharide (H2N2F2) was captured and isolated from romaine lettuce extract by a bacterial surface display system. Using electrospray ionization mass spectrometry and tandem mass spectrometry, it was shown that H2N2F2 was most likely to be a chimera of type A, H, and Lewis a HBGAs. The composition was consistent with our ELISA results using a panel of monoclonal antibodies against HBGAs. Our results revealed a possible interaction mechanism between HuNoVs and romaine lettuce. Better understanding of the interaction of HuNoVs with easily contaminated produce will ultimately aid in the control of and reduction in disease outbreaks.

CAS / MDL: 9016-45-9
研究领域: 病毒学 · 食品科学 · 分子生物学
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ADVANCED MATERIALS · 2025 · IF 26.8

Tumor-Targeting Co-Delivery of T-Cell Antigen and Camptothecin Guided by Cascade-Responsive Peptide Self-Assembly to Reshape Tumor Antigenicity for Cancer Immunotherapy

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 · 纳米医学 · 药物递送系统 · 免疫治疗 · 分子自组装
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AFRICAN JOURNAL OF BIOTECHNOLOGY · 2011 ·Vol. 8 ·期 24 · IF 0.573

Preparation and characterization of antigenic properties of gramicidin A- keyhole limpet hemocyanin and gramicidin A- ovalbumin conjugates

L Chun,Y Xiaoping,H Guangrong,W Hong

A rapid, simple and low cost procedure for preparing hapten-protein conjugates was developed using gramicidin A (GA) and two other water-soluble proteins, keyhole limpet hemocyanin (KLH) and ovalbumin (OVA). GA was a kind of antimicrobial peptides. Two lysines and a cysteine were linked to amino- terminus and carboxyl-terminus of the peptide chain, respectively, in order to form sulfhydryl groups and improve its water solubility. And the molecule weight and purity of the modified peptidechain were checked by electron spray ionization mass spectrometry (ESI-MS) and high performance liquid chromatography (HPLC). Then the activated KLH and OVA were conjugated to GA by using  4-(Nmaleimidomethyl) cyclohexane-1-carboxylic acid 3-sulfo-N-hydroxysuccinimide ester sodium salt (sulfo-SMCC) to form disulfide linkage. In order to obtain artificial antigen of GA, GA was linked to KLHand OVA by sulfo-SMCC coupling at room temperature. The conjugates of KLH-Peptide and OVAPeptide were identified by infrared and ultraviolet spectrophotometry SDS-PAGE and DTNB method, which could prove the activity of the sulfhydryl-groups. In this way, we have obtained a novel artificial immunogen and coating antigen that could be used to raise polyclonal antibody through immunized rabbits.

研究领域: 免疫学 · 生物化学
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Emerging Microbes & Infections · 2023 · IF 13.2

Th1-polarized MtrE-based gonococcal vaccines display prophylactic and therapeutic efficacy

Shuaijie Song,Shuyi Wang,Xiaoyun Jiang,Fan Yang,Shuai Gao,Xu’ai Lin,Hao Cheng,Stijn van der Veen

Global dissemination of high-level ceftriaxone-resistant Neisseria gonorrhoeae strains associated with the FC428 clone poses a threat to the efficacy ceftriaxone-based therapies. Vaccination is the best strategy to contain multidrug-resistant infections. In this study, we investigated the efficacy of MtrE and its surface Loop2 as vaccine antigens when combined with a Th1-polarizing adjuvant, which is expected to be beneficial for gonococcal vaccine development. Using in vitro dendritic cell maturation and T cell differentiation assays, CpG1826 was identified as the optimal Th1-polarizing adjuvant for MtrE and Loop2 displayed as linear epitope (Nloop2) or structural epitope (Intraloop2) on a carrier protein. Loop2-based antigens raised strongly Th1-polarized and bactericidal antibody responses in vaccinated mice. Furthermore, the vaccine formulations provided protection against a gonococcal challenge in mouse vaginal tract infection model when provided as prophylactic vaccines. Also, the vaccine formulations accelerated gonococcal clearance when provided as a single therapeutic dose to treat an already established infection, including against a strain associated with the FC428 clone. Therefore, this study demonstrated that MtrE and Loop 2 are effective gonococcal vaccine antigens when combined with the Th1-polarizing CpG1826 adjuvant.

研究领域: 微生物学 · 免疫学 · 传染病学
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SENSORS · 2020 ·Vol. 20 ·期 17 ·4912 · IF 3.275

Chemiluminescent Optical Fiber Immunosensor Combining Surface Modification and Signal Amplification for Ultrasensitive Determination of Hepatitis B Antigen

Xuexue Xu,Rongbin Nie,Jingwen Huang,Li Yang

Optical fiber based immunosensors are very attractive for biomarker detection. In order to improve the sensor response, we propose a promising strategy which combines porous-layer modification of the fiber surface and streptavidin-biotin-peroxidase nano-complex signal amplification in chemiluminescent detection. Two hepatitis B antigens, hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg), are used as the targets for analysis using the proposed sensor. Comparing to immunoassays using normal optical fiber sensors, the response of the present sensor is enhanced by a factor of 4.8 and 6.7 for detection of HBsAg and HBeAg, respectively. The limit-of-quantitation of the proposed method is as low as 0.3 fg/mL (0.01 fg/mL) with a wide linear response range of 3 fg/mL–150 ng/mL (0.1 fg/mL–160 ng/mL) for sensing HBsAg (HBeAg). Quantitative determination of HBsAg and HBeAg in human serum samples is performed, showing the applicability of the proposed method for biomarker detection.Keywords:optical fiber immunosensor;surface modification;signal amplification;hepatitis B surface antigen;hepatitis B e antigen

CAS / MDL: 57-09-0 57-13-6 78-10-4
研究领域: 生物医学工程 · 分析化学 · 医学诊断
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SENSORS AND ACTUATORS B-CHEMICAL · 2018 · IF 5.667

Three kinds of DNA-directed nanoclusters cooperating with graphene oxide for assaying mucin 1, carcinoembryonic antigen and cancer antigen 125

Yingyi Wang,Shanshan Wang,Chunsong Lu,Xiaoming Yang

Malignant tumors posed severe threat to human health, and various efforts have been contributed towards assaying tumor markers, howbeit, achieving to identify the multiple targets by one single analytical mode is in demand. Hereby, three kinds of aptamer-functionalized silver and silver/gold nanoclusters (DNA-AgNCs and DNA-Ag/AuNCs) were originally synthesized, and possessed the specific recognition ability for their corresponding targets. Specifically, the fluorescence of AgNCs or Ag/AuNCs was quenched by introducing graphene oxide (GO), and more competitive interactions between tumor markers and their aptamers occurred with the targets added, thus facilitating their fluorescence recovered. Based on AgNCs or Ag/AuNCs cooperating with GO, this sensing mode was subsequently employed for detecting mucin 1 in a linear range of 1.33–200 ng/mL with a detection limit of 0.18 ng/mL. Meanwhile, this method was also applied to examine carcinoembryonic antigen and cancer antigen 125, and showed the linear range of 6.7 ng/mL–13.3 μg/mL with a detection limit of 3.18 ng/mL for CEA, while CA125 sensing acquired a linear range of 2 ng/mL–6.7 μg/mL accompanied by a detection limit of 1.26 ng/mL. Besides, this strategy provided the potential ways to identify other tumor markers by designing their corresponding nanoclusters with the aptamers.

CAS / MDL: 7782-42-5
研究领域: 纳米技术 · 生物医学工程 · 分析化学 · 癌症研究
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