Crown Bioscience (China)

This study explores the lamination performance of wood-plastic composite boards designed for indoor decoration, aiming to enhance adhesion between a wood fiber/high-density polyethylene (HDPE) composite board and poplar wood veneer by incorporating fabrics (canvas or polyester fibers) as an intermediate layer. Traditional adhesives, such as polyvinyl acetate (PVAc) and isocyanate, were utilized to create decorative panels with a multi-interface sandwich structure. The impacts of factors such as the hot-pressing temperature, wood fiber content in the substrate, and fabric type on the performance of the panels were systematically investigated. The results indicated that the hot-pressing temperature of the substrate had minimal effect on the lamination performance. Panels that used canvas fabric as the intermediate layer and bonded with a mixed adhesive of PVAc and isocyanate exhibited superior surface bonding strength (2.76 MPa), bending properties (strength = 49.21 MPa; modulus = 3.92 MPa), and tensile properties (strength = 31.62 MPa; modulus = 1.51 GPa). The enhanced performance was attributed to the covalent bonding formed by isocyanate with canvas fabric, polyester fibers, and wood veneer, whereas PVAc primarily established physical bonds through penetration.

Abstract Background: Mouse syngeneic models are widely used to study tumor-immune interactions and evaluate the efficacy of immunotherapies. Proteins serve as a link between the genetic code and phenotype, and can better reflect the dynamic state of a cell. However, the large-scale profiling of proteomics and phosphoproteomics data using syngeneic models has been limited. This study aims to reveal molecular mechanisms underlying tumor development and therapeutic response using multi-omics data generated from syngeneic models. Methods: Untreated fresh tumor tissues (around 500 mm3) from 12 mouse syngeneic models (H22, EMT6, Hepa16, CT26, MC38, Pan02, A20, Renca, RM1, LL2, B16F10 and B16BL6) were collected. Tissues were analyzed using RNA-seq, proteomics and phosphoproteomics. Efficacies of immune checkpoint inhibitors (ICIs) including anti-PD-1 (RMP1-14), anti-PD-L1 (10F.9G2) and anti-CTLA4 (9D9 and 9H10) were tested in each model over a period of 2-3 weeks. Tumor growth inhibition (TGI) values were calculated as: TGI = 1 - ΔT(t)/ΔC(t), where ΔT(t) and ΔC(t) represent average changes in tumor volume from the start of experiment to time t in the treatment and vehicle group, respectively. Models with TGI>=0.45 for at least two ICIs were defined as “responder”, while models with TGI<=0.40 for all ICIs were defined as “non-responder”. Tumor purity scores were inferred with the ESTIMATE software. Differential Expressed Genes (DEGs), Differentially Expressed Proteins (DEPs) and Differentially Phosphorylated Sites (DPSs) were calculated with the limma package. Gene Set Enrichment Analysis (GSEA) was performed using the clusterProfiler package. Kinase Substrate Enrichment Analysis (KSEA) was finished using the KSEAapp package. Network analysis was performed with the STRINGdb package. Results: Estimation of stromal and immune cells using specific genes with transcriptomics and proteomics data revealed that B16BL6 and B16F10 models had the highest tumor purity and low percentage of immune and stromal cells, while A20 model had more immune cell infiltration, and other solid tumor models had relatively higher stromal cell percentage. Next, at RNA and protein levels, genes positively correlated with the drug efficacy were enriched in interferon related pathways and immune response pathways for all ICIs. Furthermore, Dnmt3a and Igfr2 were identified as potential resistant biomarkers for immunotherapy efficacy. Finally, a user-friendly website was designed for both direct acquisition of results generated in this study and deep exploration by simply clicking to choose combinations of parameters and generate new results. Conclusion: This study presents a comprehensive integrated multi-omics analysis using transcriptomics, proteomics and phosphoproteomics data collected from 12 widely used mouse syngeneic models, which provides insights into molecular mechanisms and pathways involved in tumor development and therapeutic response. Citation Format: Zihan Xu, Binchen Mao, Wubin Qian, Xiaobo Chen, Sheng Guo. Integrative multi-omics characterization of syngeneic tumor models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5005.

Abstract Introduction: Antibody-drug conjugates (ADCs) represent a breakthrough therapeutic class that provides tumor-targeted cytotoxicity while stimulating immune responses, offering promising potential when combined with immunotherapies and particularly with PD-1 inhibitors. Traditional xenograft tumor models developed in immunodeficient mice are employed to evaluate ADCs' anti-tumor efficacy. However, these models lack competent immune systems and human antigen expression in normal tissues, limiting their capacity to assess immune responses and toxicity. To address these limitations, we developed HuCell, mouse tumor cells engineered to express tumor associated antigen (hTAA) such as HER2, and HuGEMM, humanized for a specific drug target within mice with a functional immune system. In this study HuCell/HuGEMM humanized mouse models were developed to evaluate the efficacy of ADCs in combination with anti-PD-1 immunotherapy and toxicity. Methods: Surface expression of human HER2, Trop2, and Nectin-4 on MC-38 HuCell was verified using flow cytometry before and after inoculation on mice. 5×106 HuCells were subcutaneously inoculated into hHER2, hTrop2, hNectin4 and hHER2/hPD-1 models in C57BL/6 background or wild-type (WT) models. Tumor-bearing models were treated with monotherapy of trastuzumab-deruxtecan (T-Dxd), sacituzumab govitecan or enfortumab vedotin, or combination therapy with anti-PD-1 antibodies. For the toxicity study, 180 mg/kg T-Dxd and 100 mg/kg trastuzumab-emtansine (T-DM1) were injected into hHER2 mice weekly for two doses by intravenous injection. Results: A highly HER2-expressing HuCell line (clone #2) successfully grew in hHER2 models but not in WT models, with tumors displaying nearly 100% of human Her2 positive cells with high surface expression (2×105 molecules per cell). In dose response study, T-Dxd significantly inhibited tumor growth at 5 mg/kg and 10 mg/kg in C57BL/6-hHER2. Combination treatment of T-Dxd (4 mg/kg+2 mg/kg, QW) with Keytruda (5 mg/kg, BIW×2) resulted in a complete response rate (8/8) with 87% TGI (p<0.01) compared to T-Dxd monotherapy (7/8) with 96% TGI (p<0.001) in hHER2/PD-1 double knock in mice. In a toxicity study, T-DM1 showed liver toxicity, whereas T-Dxd did not. Both T-DM1 and T-Dxd exhibited notable hematological toxicity, consistent with clinical observations. In the Trop2 and Nectin-4 HuCell/HuGEMM studies, similar results were observed. HuGEMM models demonstrated superior positive cell rate and single-cell antigen expression levels. Furthermore, a synergistic effect was observed when PD-1 therapy was combined with monotherapy. Conclusion: HuCell and HuGEMM models provide an advanced platform to evaluate ADC drug monotherapy and combination therapies with immune checkpoint inhibitors. Additionally, they offer a sophisticated solution to assess both on-target and off-target toxicity of ADCs. Citation Format: Xiaoze Wang, Rong Wang, Kaixia Lian, Rongfei Lu, Jian Feng, Jun Zhou, Xiaolong Tu, Xinhe Feng, Jie Lin, Fuping Xu, Ludovic Bourre, Jingjing Wang. Novel humanized cell and murine models expressing tumor-associated antigens for ADC toxicity and IO combination evaluation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7270.

Accurate assessment of Newcastle disease virus (NDV) antibody titers is crucial for effective poultry disease control and surveillance. This article introduces an optimized method for preparing 4 hemagglutination units (4-HAU) antigen solution, a key component of the hemagglutination inhibition assay (HI) used in NDV serological detection. Unlike conventional methods, which involve time-consuming and undefined back-titration and adjustment steps, this approach streamlines this process by accurately measuring the HA titer using an initial series of dilutions (1:3, 1:5, 1:7, and 1:9). We also provide a specific method for adjusting or reformulating based on the back-titration results, reducing the need for repeated back-titrations. In addition, we evaluated the effect of the accuracy of the 4-HAU antigen solution on serum HI titer and found that when the titer of the 4-HAU antigen was lower than 3, it resulted in the appearance of false-positive HI samples. By providing an accurate method and minimizing computational tasks, this approach increases test efficiency and reliability, contributing to improved disease surveillance and control in poultry populations.

L’article explore la manière dont Gramsci formule son idée d’émancipation populaire. En partant d’une comparaison avec la manière libérale de concevoir la relation entre les intellectuels et le peuple, l’étude propose de reconnaître le propre de l’idée gramscienne d’émancipation populaire dans la notion d’autoconscience intellectuelle. La première partie propose une reconstruction philologique de la problématique à partir d’une série de notes des Cahiers de prison rédigées à partir de mars 1932, tandis que la seconde propose une analyse politico-philosophique du § 1 du Cahier 11.

BackgroundCanine enteric coronavirus (CECoV) is a prevalent infectious disease among dogs worldwide, yet its epidemiology in mainland China remains poorly understood. This systematic review and meta-analysis aimed to assess the prevalence of CECoV in mainland China and identify factors influencing its prevalence.MethodsA comprehensive literature search was conducted across multiple databases for studies regarding CECoV epidemiology of China. PubMed, CNKI, Wanfang, and CQVIP were searched to obtain the studies. Eligible studies were selected based on predefined criteria, and data were extracted and synthesized. The quality the studies was assessed using the JBI assessment tool. Heterogeneity was checked using I2 test statistics followed by subgroup and sensitivity analysis. Subgroup analyses were performed to explore variations in CECoV prevalence by factors such as year, region, season, health status, social housing type, gender, age, and breed. Publication bias was assessed using a funnel plot and eggers test that was followed by trim and fill analysis.ResultsA total of 27 studies involving 21,034 samples were included in the meta-analysis. The overall pooled prevalence of CECoV in mainland China was estimated to be 0.30 (95% CI 0.24–0.37), indicating persistent circulation of the virus. Subgroup analyses revealed higher prevalence rates in younger dogs, multi-dog households, apparently healthy dogs, and certain regions such as southwest China. Seasonal variations were observed, with lower prevalence rates in summer. However, no significant differences in prevalence were found by gender.ConclusionsThis study provides valuable insights into the epidemiology of CECoV in mainland China, highlighting the persistent circulation of the virus and identifying factors associated with higher prevalence rates. Continuous monitoring and surveillance efforts, along with research into accurate detection methods and preventive measures, are essential for the effective control of CECoV and mitigation of its potential impact on animal and human health.

Abstract Introduction: The development and use of therapeutic antibodies in cancer therapy has increased significantly in recent years, led by the success of approved immune checkpoint blockade antibodies targeting PD-1 and PD-L1 axis. However, obtaining more clinically relevant pharmacokinetics (PK), safety and efficacy data for antibodies is still challenging in preclinical phase. Humanized FcRn (hFcRn) transgenic mouse model has a more faithful catabolism compared to WT mice, providing more accurate and predictable PK data of innovative antibody-based therapeutics at discovery stage[1]. In this study, we sought to investigate pharmacokinetics and immunogenicity characteristics of anti-PD-1 antibody in hFcRn transgenic mice and provide guidance for its differentiation of prediction value for drug PK and safety by comparing to WT mice. Methods: Non-tumor bearing hFcRn mice and wild type C57BL/6 mice were divided into 2 groups, 5 mice were enrolled into each group. Mice were administered anti-PD-1(Nivolumab) at 10 mg/kg single dose after grouping by intravenous (IV) injection. Blood samples at 12 timepoints (15min, 6h, 1, 2, 4, 7, 10, 14, 21, 28, 35, 42 days) post-dosing were collected for PK and Anti-Drug Antibody (ADA) analysis by MSD and ELISA. Results: Nivolumab clearance in hFcRn mice followed a typical linear profile with rapid distribution phase and slow elimination phase (t1/2 = 350 to 400 h). While the PK profile in C57BL/6 mice displayed non-linear clearance and very short elimination phase (t1/2 = 45 to 50 h). This data demonstrated that hFcRn mice have better correlated half-life with human (Nivolumab single dose by IV with 10mg/kg, t1/2 = 595 h) [2]. ADA analysis revealed that it was produced starting from Day 10 in wild type C57BL/6 mice and the frequency of ADA induced by Nivolumab in wild type mice (2/5) was higher than hFcRn mice (0/5). The variation of Nivolumab level was correlated with ADA production in wild type mice. This suggested hFcRn shows lower immunogenicity than wild type mice for human IgG drug and can potentially improve negative effect of ADA interference on PK evaluation. Conclusion: The result of this study demonstrated that the PK data in hFcRn mouse model was more predictive of human PK profile compared to wild type C57BL/6 mice. This advances innovation in antibody-based therapeutics and translational applications, with improved PK, safety and efficacy evaluation for preclinical human IgG drug development in cancer therapy.

Abstract Introduction Immuno-oncology drug treatments, including immune checkpoint inhibitors, represent a huge promise for cancer patients and have been clinically approved for some cancer indications. However, patient response rates stay relatively low (about 10-20% responders across indications) hampering the success of such drugs in clinical trials. In addition, current in vitro and in vivo pre-clinical models often lack the (immunological) complexity necessary to predict the clinical effectiveness of such drugs or drug combinations. To bridge this gap in translational models, we have recently developed the 3D Ex vivo Patient Tissue (EVPT) platform. The EVPT platform is leveraging short-term 3D ex vivo tumor culture system containing micro-tissues generated from fresh human tumor material and high content imaging analysis. The platform is preserving the innate tumor microenvironment including resident immune cells, which are crucial for addressing immunological drug responses. In this study we aimed to further boost immune compartment of the assay by addition of autologous immune cells (PBMCs) isolated from whole blood of the patient in parallel with ex vivo tumor processing. Methods Patient tumor tissues from resected NSCLC and muscle-invasive bladder cancer (MIBC) tumors and matching peripheral blood were obtained from commercial tissue providers and processed within 24 hours to preserve the TME. PBMCs were isolated from whole blood and pre-stained with cell tracker. Fresh, minimally processed tumor material was embedded in a protein-rich hydrogel with or without matching PBMCs and exposed to mono- and combination immunotherapies at various doses. Next, the phenotypic screening using our proprietary automated HCI analysis platform was performed. Where applicable, IHC biomarker, flow cytometry and cytokine measurements were performed on fixed tissues or culture supernatants. Results 3D ex vivo co-cultures were executed in 22 NSCLC and 5 MIBC patient samples. Immunological treatment responses varied between tested patients. When comparing co-culture to mono-culture conditions, one third of the samples showed baseline killing associated with PBMCs addition. About 20% of tissues from both indications responded to antiPD1 treatment (Pembrolizumab) and on average 50% of tissues responded to immunostimulatory control SEA. Overall best effects were observed for one test article that was used in three doses in combination with antiPD1. Five out five tested NSLCLC samples showed functional responses in these conditions as wells as two out five MIBC samples. In addition, it induced immunostimulatory effects on the PBMCs in the assay – increased numbers and tumor infiltration rates compared to vehicle control. Conclusions 3D Ex vivo Patient Tissue platform combined with autologous PBMCs offers supplementary readouts such as tumor infiltration and immune cell proliferation while providing TME-rich environment for functional immune-oncology drug testing. Citation Format: Niels Meesters, Sander Basten, Ezgi Kaya Aksoy, Mariusz Madej, Kuan Yan, Emma Spanjaard, Leo S. Price, Nataliia Beztsinna. Quantification of immune-oncology drug responses in autologous co-cultures of ex vivo patient tumor tissues with PBMCs [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_B16.

Breakthroughs in cancer treatment with immunotherapeutics have provided long-term patient benefits for many different types of cancer. However, complete response is not achieved in many patients and tumor types, and the mechanisms underlying this lack of response are poorly understood. Despite this, numerous new targets, therapeutics, and drug combinations are being developed and tested in clinical trials. Preclinical models that recapitulate the complex human tumor microenvironment and the interplay between tumor and immune cells within the cancer-immunity cycle are needed to improve our understanding and screen new therapeutics for efficacy and safety/toxicity. Humanized mice, encompassing human tumors and human immune cells engrafted on immunodeficient mice, have been widely used for many years in immuno-oncology, with developments to improve both the humanization and the translational value central to the next generation of models. In this overview, we discuss recent advances in humanized models relevant to immuno-oncology drug discovery, the advantages and limitations of such models, the application of humanized models for efficacy and safety assessments of immunotherapeutics, and the potential opportunities. © 2023 Crown Bioscience. Current Protocols published by Wiley Periodicals LLC.

Patient-derived tumor xenograft (PDX)/organoid (PDO), driven by cancer stem cells (CSC), are considered the most predictive models for translational oncology. Large PDX collections reflective of patient populations have been created and used extensively to test various investigational therapies, including population-trials as surrogate subjects in vivo. PDOs are recognized as in vitro surrogates for patients amenable for high-throughput screening (HTS). We have built a biobank of carcinoma PDX-derived organoids (PDXOs) by converting an existing PDX library and confirmed high degree of similarities between PDXOs and parental PDXs in genomics, histopathology and pharmacology, suggesting “biological equivalence or interchangeability” between the two. Here we demonstrate the applications of PDXO biobank for HTS “matrix” screening for both lead compounds and indications, immune cell co-cultures for immune-therapies and engineering enables in vitro/in vivo imaging. This large biobank of >550 matched pairs of PDXs/PDXOs across different cancers could become powerful tools for the future cancer drug discovery.