基因工程小分子抗体研究进展

自从七十年代杂交瘤技术问世以来,人们获得了多种抗肿瘤的单克隆抗体(McAb),用单克隆抗体为载体,接上药物、毒素或放射性同位素而形成免疫交联物,用于肿瘤的导向诊断和导向治疗,一直是一个极有吸引力的前景。McAb标记上同位素用于肿瘤定位诊断的实验与临床研究取得了令人鼓舞的成绩,但导向治疗的临床研究结果却远远低于人们的期望值,主要原因有以下两方面。首先是所用的小鼠单位往往导致人抗鼠抗体反应,一次注射抗体有50％的病人产生抗抗体;其次是     

抗肿瘤基因工程单链抗体导向药物研究进展

过去30年肿瘤治疗取得了极大的进步,基因工程技术推动了肿瘤免疫治疗的发展,以基因工程为基础的单链抗体导向药物成为肿瘤免疫治疗的新热点,其用于治疗肿瘤的药物研究取得了重大进展。研究表明,基因工程单链抗体导向药物能特异性结合肿瘤相关靶点,对肿瘤细胞有选择性的杀伤作用,并在动物实验中有显著的疗效。基因工程单链抗体导向药物在肿瘤治疗中将发挥重要作用,具有广阔的应用前景。综述了这一领域的发展,并对其前景进行了预测。     

抗肿瘤基因工程单链抗体导向药物

过去30年肿瘤治疗取得了极大的进步,基因工程技术推动了肿瘤免疫治疗的发展,以基因工程为基础的单链抗体导向药物成为肿瘤免疫治疗的新热点,其用于治疗肿瘤的药物研究取得了重大进展.研究表明,基因工程单链抗体导向药物能特异性结合肿瘤相关靶点,对肿瘤细胞有选择性的杀伤作用,并在动物实验中有显著的疗效.基因工程单链抗体导向药物在肿瘤治疗中将发挥重要作用,具有广阔的应用前景.综述了这一领域的发展,并对其前景进行了预测.     

IgY抗体作为导向载体对消化系统肿瘤的选择性识别作用研究

用生物治疗方法治疗肿瘤已被视为肿瘤治疗的第四大疗法,其主要是免疫治疗．包括抗体与偶合物,肿瘤疫苗等。而要想获得有效的肿瘤治疗药物．其关键是要寻找小型化的、高效的导向载体。我们的实验室以低分化腺胃癌的P110癌蛋白作为抗原,免疫SPF鸡,从卵黄中提取抗体IgY作为植物毒素的导向性载体;实验结果证明,IgY能特异性地选择识别消化系统的肿瘤组织,为进一步研究肿瘤的导向药物提供了另一理论依据。     

肿瘤导向治疗研究进展

特异性地杀伤肿瘤细胞并降低对正常细胞的毒副作用是各种导向治疗方法的共同目标。本文综述了前体药物疗法,免疫毒素,基因疗法,以肿瘤增殖转移过程中的关键分子为靶的导向治疗,生物素－亲和素系统等导向治疗的研究进展。     

双特异性抗体的制备与应用

双特异性抗体是指通过化学交联、细胞工程和基因工程方法制备的一种可以在体内、外特异识别两种抗原并能与之结合产生生物学效应的抗体分子,在免疫学检测与肿瘤药物导向治疗和介导细胞毒作用中应用广泛。近年来,对双特异性抗体制备与应用的研究越来越深入,本文仅就这两方面研究的最新进展作一介绍。     

单链抗体的生物学特性及应用前景

自从 70年代德国学者克勒 (Kohler)和英国学者米尔斯坦 (Milstein)利用细胞融合技术首次成功制备单克隆抗体 ,并制备杂交瘤技术以来 ,不仅促进了整个生命科学基础研究领域的发展 ,而且给抗体研究及应用带来了突破。单克隆抗体在许多疾病临床诊断、治疗、预防和蛋白提纯等方面日益显示出重要作用和广阔的应用前景 ,特别是众多选择良好的抗各种肿瘤单抗体的制备 ,使导向药物的研究领域重新受到人们的重视。据估计到本世纪末以抗体为基础的诊断和治疗试剂在全世界的销售额可高达60亿美元。然而 ,传统的单克隆抗体由于其分子本身的结构问题在肿…     

生长抑素受体介导的肿瘤靶向治疗

许多肿瘤,如神经内分泌肿瘤、甲状腺癌、乳腺癌等能高表达生长抑素受体,从而为生长抑素及其类似物的治疗提供了靶点。生长抑素受体介导的肿瘤靶向治疗主要包括放射性核素治疗、放射导向手术治疗、细胞毒素治疗和溶瘤病毒治疗。目前,生长抑素受体介导的放射性核素治疗已应用于神经内分泌肿瘤,尤其在胃肠胰神经内分泌肿瘤的诊断和治疗中占据重要地位。另外,生长抑素受体介导的放射导向手术治疗、细胞毒素治疗和溶瘤病毒治疗的潜在价值也越来越引起研究者们的重视。本文通过查阅近五年来关于生长抑素受体介导的肿瘤靶向治疗的国内外文献,综述了生长抑素受体介导的肿瘤靶向治疗的最新研究进展。     

双特异性抗体及其在肿瘤治疗中的应用

双特异性抗体（BsAb）是改造抗体治疗效果的发展方向之一,现已成为抗体工程研究领域的热点。在过去20年的研究中．研究人员看到了常规BsAb的潜能以及它的不足。随着分子生物学技术的迅速发展,出现了利用基因工程手段构建的BsAb的多种模式,并且有多种BsAb制剂已经用于肿瘤的初期临床诊断和治疗。该文对BsAb最新的研究进展和肿瘤治疗中的应用进行了阐述。     

导读北大核心CSCD

本期导读主题:基因诊断技术、抗新冠抗体药物、高通量药物筛选技术、纳米抗体、多组学肿瘤药物敏感性预测、植物质体转基因技术、肠道微生物与疾病。以基因工程为基础、细胞工程为导向的现代生物技术在医药领域的广泛应用,被称之为现代医药生物技术。现代医药生物技术在疾病的诊断、预防和治疗及生物技术药物的研发中的应用,促进了诸如传染病、恶性肿瘤、心脑血管疾病等重大疾病在诊断、预防、治疗上的技术革命,已成长为现代工业的支柱产业之一的生物医药产业,服务于人类的健康事业。     

Aerosol gene therapy

Gene therapy is a novel field of medicine that holds tremendous therapeutic potential for a variety of human diseases. Targeting of therapeutic gene delivery vectors to the lungs can be beneficial for treatment of various pulmonary diseases such as lung cancer, cystic fibrosis, pulmonary hypertension, alpha-1 antitrypsin deficiency, and asthma. Inhalation therapy using formulations delivered as aerosols targets the lungs through the pulmonary airways. The instant access and the high ratio of the drug deposited within the lungs noninvasively are the major advantages of aerosol delivery over other routes of administration. Delivery of gene formulations via aerosols is a relatively new field, which is less than a decade old. However, in this short period of time significant developments in aerosol delivery systems and vectors have resulted in major advances toward potential applications for various pulmonary diseases. This article will review these advances and the potential future applications of aerosol gene therapy technology.     

The biology and future prospects of antivirulence therapies

The emergence and increasing prevalence of bacterial strains that are resistant to available antibiotics demand the discovery of new therapeutic approaches. Targeting bacterial virulence is an alternative approach to antimicrobial therapy that offers promising opportunities to inhibit pathogenesis and its consequences without placing immediate life-or-death pressure on the target bacterium. Certain virulence factors have been shown to be potential targets for drug design and therapeutic intervention, whereas new insights are crucial for exploiting others. Targeting virulence represents a new paradigm to empower the clinician to prevent and treat infectious diseases.     

Radiopharmaceuticals targeting PSMA for imaging and/or therapy

Targeting the Prostate Specific Membrane Antigen (PSMA) is becoming increasingly more important for the management of prostate cancer patients at various stages. This review article describes selected radiolabelled PSMA inhibitors with optimized radiopharmaceutical properties for imaging and/or therapy.     

Cancer targeting gene-viro-therapy specific for liver cancer by α-fetoprotein-controlled oncolytic adenovirus expression of SOCS3 and IL-24

The combination of gene therapy and virotherapy for cancer treatment has received close attention and has become a trend in the field of cancer biotherapy. A strategy called 'Cancer Targeting Gene-Viro-Therapy' (CTGVT) or 'Gene Armed Oncolytic Viral Therapy' (GAOVT) has been proposed, in which an antitumor gene is inserted into an oncolytic viral vector. In our previous study, a dual-regulated oncolytic adenovirus with enhanced safety for normal cells and strict liver cancer-targeting ability, designated Ad?enAFP?E1A?E1B (Δ55) (briefly Ad?enAFP?D55), was successfully constructed. In the current work, interleukin-24 (IL-24) and suppressor of cytokine signaling 3 (SOCS3) genes were packaged into Ad?enAFP?D55. The new constructs, Ad?enAFP?D55-(IL-24) and Ad?enAFP?D55-(SOCS3), showed improved tumoricidal activity in hepatoma cell lines compared with the oncolytic viral vector Ad?enAFP?D55. The co-administration of Ad?enAFP?D55-(IL-24) and Ad?enAFP?D55-(SOCS3) showed much better antitumor effect than Ad?enAFP?D55-(IL-24) or Ad?enAFP?D55-(SOCS3) alone both in vitro and in a nude mouse xenograft model. Moreover, our results also showed that blockade of the Jak/Stat3 pathway by Ad?enAFP?D55-(SOCS3) infection in HuH-7 cells could down-regulate some anti-apoptosis proteins, such as XIAP, Bcl-xL, and survivin, which might sensitize the cells to Ad?enAFP?D55-(IL-24)-induced apoptosis. These results indicate that co-administration of Ad?enAFP?D55-(IL-24) and Ad?enAFP?D55-(SOCS3) may serve as a candidate therapeutic approach for the treatment of liver cancer.     

Targeting gene-virotherapy of cancer

Our purpose is to completely elimination of xenograft tumor in animal tumor model in order to work out a protocal for the cure of patient. Gene therapy and viral therapy for cancer have got some therapeutic effects, but both have no great breakthrough. Therefore, we worked out a new strategy called Targeting Gene-Virotherapy of Cancer which is a combination of the advantage of gene therapy and virotherapy. This new strategy has stronger antitumor effect than either of them alone. A tumor specific replicative adenovirus vector ZD55 (E1B 55KD deleted Adv.) which is similar to ONYX-015 in targeting fuction but significant different in construction was produced and various single therapeutic gene was inserted into ZD55. Now such a conception as Targeting Gene-Virotherapy of Cancer was raised and systemically studied before, although there are some works on ONYX-015-tk, -cd or cd/-tk etc. separately. The antitumor effect of ZD55-Gene (for example IL-24 gene) is much better than ZD55 (virotherapy) alone and hundred fold high than that of Ad-IL-24 (gene therapy) alone. ZD55-IL-24 was in preclinal studying in the ZD55-IL-24 therapy, completely elimination of tumor mass was occurred in some mice but not in all mice, that means one gene was not effictive enough to eliminate all the tumor mass in all mice. Therefore two genes with compensative or synergetic effect were inserted into ZD55 separately and used in combination. This strategy was called Targeting Dual Gene-Virotherapy of Cancer (with PCT patent). Then much better results were obtained and all the xenograft tumor masses were completely eliminated in all mice, if two suitable genes were chosen. On the basis of the initiation of two gene results, it was thought about that using two tumors promoter to control the virus vector will be better for the targeting effect and the safty of the drugs. Then double tumor controlled virus vector harboring two genes for cancer therapy was worked out. Better results have been obtained and another patent has been applied. This antitumor strategy could be used to kill all the tumor cells completely in all mice with minimum damage to normal cells.     

“Targeting the absence” and therapeutic engineering for cancer therapy

The Gotham Prize was awarded to Alex Varshavsky for “Targeting the absence”, a strategy employing negative targets of cancer therapy. This is a brilliant example of therapeutic engineering: designing a sequence of events that leads to the selective killing of one type of cell, while sparing all others. A complex molecular device (Varshavsky’s Demon) examines DNA, recognizes the present target in normal cells and kills cancer cells. The strategy is limited by the delivery (transfection or infection) of DNA-based devices into each cell of our body. How can we overcome this limitation? Can therapeutic engineering be applied to small drugs? Can each small molecule reach a cell separately and, once in a cell, exert orchestrated action governed by cellular context? Here I describe how a combination of small drugs can acquire a demonic power to check, choose and selectively kill. The cytotoxicity is restricted to cells lacking (or having) one of the targets. For example, in the presence of a normal target, one drug can cancel the cytotoxic action of another drug. And by increasing a number of targets, we can increase the precision and power of such ‘restrictive’ combinations. Here I discuss restrictive combinations of currently available drugs that could be tested in clinical trials. Could then these combinations cure cancer today? And what does ‘cure’ really mean? This article suggests the answer.     

One shoot,three birds: Targeting NEK2 orchestrates chemoradiotherapy,targeted therapy,and immunotherapy in cancer treatment

Combinational therapy has improved the cancer therapeutic landscape but is associated with a concomitant increase in adverse side reactions. Emerging evidence proposes that targeting one core target with multiple critical roles in tumors can achieve combined anti-tumor effects. This review focuses on NEK2, a member of serine/threonine kinases, with broad sequence identity to the mitotic regulator NIMA of the filamentous fungus Aspergillus nidulans. Elevated expression of NEK2 was initially found to promote tumorigeneses through abnormal regulation of the cell cycle. Subsequent studies report that NEK2 is overexpressed in a broad spectrum of tumor types and is associated with tumor progression and therapeutic resistance. Intriguingly, NEK2 has recently been revealed to mediate tumor immune escape by stabilizing the expression of PD-L1. Targeting NEK2 is thus becoming a promising approach for cancer treatment by orchestrating chemoradiotherapy, targeted therapy, and immunotherapy. It represents a novel strategy for inducing combined anti-cancer effects using a mono-agent.     

靶向肿瘤治疗的腺相关病毒载体

靶向性是肿瘤治疗取得成功的关键因素。病毒载体用于治疗肿瘤的过程中必须要求特异性作用于肿瘤细胞的同时降低对正常细胞的毒性。腺相关病毒(adeno-associated virus,AAV)较其他病毒载体具有免疫原性小、宿主范围广和介导基因可长期表达等优点,因此得到了广泛的应用。然而,AAV载体针对肿瘤的靶向性一直是近年研究的热点和难点。现就AAV载体治疗肿瘤的概况和靶向策略以及其安全性等方面作一综述。