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期刊论文 6

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临床前大动物实验 1

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human umbilical cord-derived mesenchymal stem cells to differentiate into sweat gland-like cells: a preclinical

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《医学前沿（英文）》 2013年 第7卷 第3期   页码 345-353 doi: 10.1007/s11684-013-0282-2

摘要：

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) possess various advantageous properties, including self-renewal, extended proliferation potential, multi-lineage differentiation potential and capacity for differentiating into sweat gland-like cells in certain conditions. However, little is known about the effect of clinical-grade culture conditions on these properties and on the differentiative potential of hUC-MSCs. In this study, we sought to investigate the properties of hUC-MSCs expanded with animal serum free culture media (ASFCM) in order to determine their potential for differentiation into sweat gland-like cells. We found that primary cultures of hUC-MSCs could be established with ASFCM. Moreover, cells cultured in ASFCM showed vigorous proliferation comparable to those of cells grown in classical culture conditions containing fetal bovine serum (FBS). Morphology of hUC-MSCs cultured in ASFCM was comparable to those of cells grown under classical culture conditions, and hUC-MSCs grown in both of the two culture conditions tested showed the typical antigen profile of MSCs—positive for CD29, CD44, CD90, and CD105, and negative for CD34 and CD45, as expected. Chromosomal aberration assay revealed that the cells were stable after long-term culture under both culture conditions. Like normal cultured MSCs, hUC-MSCs induced under ASFCM conditions exhibited expression of the same markers (CEA, CK14 and CK19) and developmental genes (EDA and EDAR) that are characteristic of normal sweat gland cells. Taken together, our findings indicate that the classical culture medium used to differentiate hUC-MSCs into sweat gland-like cells can be replaced safely by ASFCM for clinical purposes.

关键词： umbilical cord     mesenchymal stem cells     sweat gland     preclinical    

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non-ligand-blocking agonistic anti-OX40 antibody, exhibits superior immune activation and antitumor effects in preclinical

《医学前沿（英文）》 doi: 10.1007/s11684-023-0996-8

摘要： OX40 is a costimulatory receptor that is expressed primarily on activated CD4+, CD8+, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40–OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.

关键词： BGB-A445     OX40     agonistic antibody     OX40L noncompetitive    

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Patient-derived xenograft platform of OSCC: a renewable human bio-bank for preclinical cancer research

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《医学前沿（英文）》 2016年 第10卷 第1期   页码 104-110 doi: 10.1007/s11684-016-0432-4

摘要：

Advances in next-generation sequencing and bioinformatics have begun to reveal the complex genetic landscape in human cancer genomes, including oral squamous cell carcinoma (OSCC). Sophisticated preclinical models that fully represent intra- and inter-tumoral heterogeneity are required to understand the molecular diversity of cancer and achieve the goal of personalized therapies. Patient-derived xenograft (PDX) models generated from human tumor samples that can retain the histological and genetic features of their donor tumors have been shown to be the preferred preclinical tool in translational cancer research compared with other conventional preclinical models. Specifically, genetically well-defined PDX models can be applied to accelerate targeted antitumor drug development and biomarker discovery. Recently, we have successfully established and characterized an OSCC PDX panel as part of our tumor bio-bank for translational cancer research. In this paper, we discuss the establishment, characterization, and preclinical applications of the PDX models. In particular, we focus on the classification and applications of the PDX models based on validated annotations, including clinicopathological features, genomic profiles, and pharmacological testing information. We also explore the translational value of this well-annotated PDX panel in the development of co-clinical trials for patient stratification and treatment optimization in the near future. Although various limitations still exist, this preclinical approach should be further tested and improved.

关键词： patient-derived xenograft models     personalized medicine     co-clinical trial     patient stratification     oral squamous cell carcinoma    

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软骨组织工程研究进展——我们的经验与未来展望

刘豫, 周广东, 曹谊林

《工程（英文）》 2017年 第3卷 第1期   页码 28-35 doi: 10.1016/J.ENG.2017.01.010

摘要：

软骨缺损难以自行修复，组织工程是实现软骨再生的理想途径。目前，组织工程软骨主要有两类用途：一是用于骨科或关节外科，修复关节表面或半月板部位的软骨缺损，实现关节运动功能的重建；二是用于整形或头颈外科，修复耳廓、气管、睑板、鼻、喉等具有特殊形态及功能的软骨缺损。不同应用目标的组织工程软骨，其构建方法和所面临的挑战，以及临床转化进程均会有很大差别。本文旨在针对上述两大应用目标，结合我们团队在研究过程中所建立的观点及积累的经验，对组织工程软骨目前的主要研究进展和所面临的挑战，以及未来的发展方向做一简要总结。

关键词： 软骨组织工程     临床前大动物实验     临床转化     骨科     整形外科    

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Preclinical characterization and comparison between CD3/CD19 bispecific and novel CD3/CD19/CD20 trispecific

《医学前沿（英文）》 2022年 第16卷 第1期   页码 139-149 doi: 10.1007/s11684-021-0835-8

摘要： The CD19-targeting bispecific T-cell engager blinatumomab has shown remarkable efficacy in patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. However, several studies showed that blinatumomab has a short plasma half-life due to its low molecular weight, and thus its clinical use is limited. Furthermore, multiple trials have shown that approximately 30% of blinatumomab-relapsed cases are characterized by CD19 negative leukemic cells. Here, we design and characterize two novel antibodies, A-319 and A-2019. Blinatumomab and A-319 are CD3/CD19 bispecific antibodies with different molecular sizes and structures, and A-2019 is a novel CD3/CD19/CD20 trispecific antibody with an additional anti-CD20 function. Our in vitro, ex vivo, and in vivo experiments demonstrated that A-319 and A-2019 are potent antitumor agents and capable of recruiting CD3 positive T cells, enhancing T-cell function, mediating B-cell depletion, and eventually inhibiting tumor growth in Raji xenograft models. The two molecules are complementary in terms of efficacy and specificity profile. The activity of A-319 demonstrated superior to that of A-2019, whereas A-2019 has an additional capability to target CD20 in cells missing CD19, suggesting its potential function against CD19 weak or negative CD20 positive leukemic cells.

关键词： B-cell acute lymphoblastic leukemia     bispecific antibody     trispecific antibody     CD19     CD20    

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Artificial Bear Bile: A Novel Approach to Balancing Medical Requirements and Animal Welfare

Yong Li,Yuhong Huang,Nan Feng,Heping Zhang,Jing Qu,Shuanggang Ma,Yunbao Liu,Jiang Li,Shaofeng Xu,Ling Wang,Mi Zhang,Jie Cai,Weiping Wang,Ru Feng,Hang Yu,Bo Yu,Dailiang Liang,Heping Qin,Suxiang Luo,Yanfen Li,

《工程（英文）》 doi: 10.1016/j.eng.2023.09.017

摘要： Bear bile has been a valuable and effective medicinal material in traditional Chinese medicine (TCM) for over 13 centuries. However, the current practice of obtaining it through bear farming is under scrutiny for its adverse impact on bear welfare. Here, we present a new approach for creating artificial bear bile (ABB) as a high-quality and sustainable alternative to natural bear bile. This study addresses the scientific challenges of creating bear bile alternatives through interdisciplinary collaborations across various fields, including resources, chemistry, biology, medicine, pharmacology, and TCM. A comprehensive efficacy assessment system that bridges the gap between TCM and modern medical terminology has been established, allowing for the systematic screening of therapeutic constituents. Through the utilization of chemical synthesis and enzyme engineering technologies, our research has achieved the environmentally friendly, large-scale production of bear bile therapeutic compounds, as well as the optimization and recomposition of ABB formulations. The resulting ABB not only closely resembles natural bear bile in its composition but also offers advantages such as consistent product quality, availability of raw materials, and independence from threatened or wild resources. Comprehensive preclinical efficacy evaluations have demonstrated the equivalence of the therapeutic effects from ABB and those from commercially available drained bear bile (DBB). Furthermore, preclinical toxicological assessment and phase Ⅰ clinical trials show that the safety of ABB is on par with that of the currently used DBB. This innovative strategy can serve as a new research paradigm for developing alternatives for other endangered TCMs, thereby strengthening the integrity and sustainability of TCM.

关键词： Artificial bear bile     Chemical profile     Formula optimization     Pharmacodynamic consistency     Preclinical toxicological assessment    

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标题 作者 时间 类型 操作

human umbilical cord-derived mesenchymal stem cells to differentiate into sweat gland-like cells: a preclinical

null

期刊论文

non-ligand-blocking agonistic anti-OX40 antibody, exhibits superior immune activation and antitumor effects in preclinical

期刊论文

Patient-derived xenograft platform of OSCC: a renewable human bio-bank for preclinical cancer research

null

期刊论文

软骨组织工程研究进展——我们的经验与未来展望

刘豫, 周广东, 曹谊林

期刊论文

Preclinical characterization and comparison between CD3/CD19 bispecific and novel CD3/CD19/CD20 trispecific

期刊论文

Artificial Bear Bile: A Novel Approach to Balancing Medical Requirements and Animal Welfare

Yong Li,Yuhong Huang,Nan Feng,Heping Zhang,Jing Qu,Shuanggang Ma,Yunbao Liu,Jiang Li,Shaofeng Xu,Ling Wang,Mi Zhang,Jie Cai,Weiping Wang,Ru Feng,Hang Yu,Bo Yu,Dailiang Liang,Heping Qin,Suxiang Luo,Yanfen Li,

期刊论文