溶瘤单纯疱疹病毒抗肿瘤作用及其机理研究

目前,已有溶瘤病毒在临床治疗上应用,是一种有效的癌症免疫治疗方法。近年来研究人员对单纯疱疹病毒的研究越来越广泛,尤其是Ⅰ型单纯疱疹病毒。为了探索溶瘤单纯疱疹病毒抗肿瘤作用及其机理,从单纯疱疹病毒的生物学特点,溶瘤单纯疱疹病毒的抗肿瘤机制,溶瘤单纯疱疹病毒的临床应用及其局限性等方面进行归纳整理。研究表明,溶瘤病毒通过多步法包括直接裂解肿瘤细胞,诱导细胞毒性或凋亡致敏细胞因子以及促进抗肿瘤T细胞应答来达到抗肿瘤的作用。增强溶瘤治疗期间的免疫反应可增强其抗肿瘤效果。溶瘤病毒在肿瘤治疗方面已经成为一种新兴制剂。     

溶瘤病毒的肿瘤治疗作用研究

通过探讨几种溶瘤病毒包括溶瘤新城疫病毒、溶瘤单纯疱疹病毒、溶瘤腺病毒和溶瘤痘病毒等治疗肿瘤的作用,为溶瘤病毒应用于肿瘤治疗提供新的启示。     

肿瘤疫苗的研究概况及进展

根据肿瘤免疫理论，人们设计了各种肿瘤疫苗，包括肿瘤细胞疫苗，肿瘤核酸疫苗和肿瘤基因工程疫苗，用于增加肿瘤的免疫原性和提高机体的抗肿瘤免疫反应。随着肿瘤免疫理论的发展，应用肿瘤疫苗对癌症患者进行主动特异性免疫治疗取得了一系列可喜的成果。本文对近年来肿瘤疫苗的研究作一简要综述。     

肿瘤疫苗的研究进展

肿瘤疫苗作为肿瘤主动性免疫治疗的重要手段,随着分子生物学的发展和基因工程技术的出现,其研究有了很大的飞跃.本文从肿瘤基因疫苗、转基因疫苗、树突状细胞与瘤苗、热休克蛋白—肽复合物肿瘤疫苗等几个方面综述肿瘤疫苗的部分研究进展.     

癌疫苗研究的进展

一、T细胞在抗肿瘤免疫中的重要性近年的大量研究表明,机体对肿瘤的免疫主要为细胞免疫,T细胞在疫苗为基础的肿瘤免疫治疗中具有重要作用。T细胞可识别癌细胞表达的三类肿瘤特异抗原:(1)突变或重排的癌基因产物和突变的抗癌基因产物。由于这些抗原绝大多数存在于细胞内,因此抗体无法发挥治疗作用,而T细胞却可特异地识别具有这类产物的肿瘤细胞。目前已在人体和鼠体上分离到针对BCR-abl、突变的ras和p53的特异性T细胞。但目前的问题是,由于不同肿     

2022年肿瘤免疫研究热点回眸

肿瘤免疫治疗已成为继手术、放疗、化疗之后的第四类肿瘤治疗方法，为当今国际研究的热点领域。在肿瘤免疫治疗新时代，以免疫检查点抑制剂、基因工程化修饰免疫细胞为代表的免疫疗法被认为具有广阔前景。概述了2022年肿瘤免疫治疗领域研究的热点及关键进展，包括嵌合抗原受体T细胞（CAR-T）在实体瘤治疗中的突破、维持记忆性T细胞生存和功能新机制的发现、改善肿瘤免疫抑制微环境提高免疫治疗疗效的深入探究以及瘤内微生物对抗肿瘤免疫反应的重要影响作用。     

利用肿瘤抗原多肽疫苗进行肿瘤的免疫治疗

利用肿瘤抗原多肽疫苗进行肿瘤的临床免疫治疗已成为肿瘤根除性治疗的重要发展方向.随着诱导机体免疫应答的各类不同肿瘤抗原的不断发现,多种肿瘤多肽疫苗已进入临床试验,并取得一定的效果.但高效广谱的疫苗还有待于进一步研究.文中总结了设计选用肿瘤多肽疫苗的依据和原则,着重阐述了用作疫苗的肿瘤抗原的选择及其发展方向,为研究肿瘤抗原多肽疫苗提供参考.     

肿节风总黄酮甙对带瘤小鼠免疫功能的影响

在我们和北京市一些医院协作以中草药治疗肿瘤工作中,看到两个现象:一是某些中草药如肿节风和扶正药物能促进肿瘤患者免疫功能。二是中晚期病人经免疫治疗后,尽管可以短期使其免疫功能上升,但难于保持下去。因为在肿瘤进行性生长过程中,带瘤机体所产生的免疫抑制因子,有效地抑制了免疫系统对肿瘤的监视和抑制作用。使免疫治疗效     

细胞因子诱导的NK细胞过继免疫治疗恶性肿瘤的初步应用

目的　采集不同类型恶性肿瘤患者外周血,扩增CINK细胞,并观察自体CINK细胞过继免疫治疗的疗效和安全性.方法　利用抗CD3 单抗、IL-2、PHA从9 例肿瘤患者PBMC中诱导扩增CINK细胞,2 周左右开始自体回输.结果　CINK细胞经培养后细胞总数和CD3- CD56+NK细胞均获大量增殖.肿瘤患者经自体CINK 细胞免疫治疗后, CD3、CD4 T 细胞、NK 细胞、CD4/CD8的比例均显著提高(P<0.01),睡眠、食欲等指标也有相应改善,治疗过程中未见副作用. 结论　自体CINK细胞过继免疫治疗可以显著提高患者免疫功能,改善患者生活质量,且副作用小.     

人乳头瘤病毒疫苗的研究策略及最新进展

人乳头瘤病毒（HPV）的持续感染与多种皮肤粘膜肿瘤密切相关，研制有效的病毒疫苗成为研究者的共同目标。本文系统综述了人乳头瘤病毒疫苗在预防和治疗两方面的研究策略以及动物和临床试验的新进展，主要包括旨在预防高危型病毒感染的二价疫苗，临床试验，交叉中和表位的研究，增强治疗性疫苗免疫原性的新尝试以及树突状细胞在病毒感染局部免疫作用中的新发现。     

自体瘤苗的研究进展

恶性肿瘤发病率逐年增高,自体瘤苗的研制在肿瘤治疗领域取得了长足的进展.研究认为,主动特异性免疫治疗是肿瘤治疗的主要发展方向之一.     

CD8<Superscript>+</Superscript> T cell response mediates the therapeutic effects of oncolytic adenovirus in an immunocompetent mouse model

The role of anti-tumor immune responses in oncolytic adenoviral therapy has not been well studied due to lack of efficacious tu- mor model in immunocompetent mice.Here,we evaluated the contributions of immune components to the therapeutic effects of oncolytic adenoviruse in an immunocompetent murine tumor model permissive for infection and replication of adenovirus.We found that CD8+T cells were critical mediator for antitumor efficacy by oncolytic adenovirus.Intratumoral viral therapy induced intensive infiltration of CD8+T cells in tumor,increased tumor-specific IFN-?(interferon-?)production and CTL(cytotoxic T lymphocyte)activity of lymphocytes,and generated a long-term tumor-specific immune memory.Boosting CD8+T cell responses by agonistic anti-4-1BB(cluster differentiation 137,CD137)antibody showed synergistic anticancer effects with oncolytic viro- therapy.Our results provide insight into antitumor mechanisms of oncolytic adenovirus in addition to their direct oncolytic effect.     

Xenogeneic homologous genes, molecular evolution and cancer therapy

Cancer is one of the main causes for death of human beings to date, and cancer biotherapy (mainlyimmunotherapy and gene therapy) has become the most promising approach after surgical therapy, radiotherapy andchemotherapy. However, there are still many limitations on cancer immunotherapy and gene therapy; therefore great ef-fort is being made to develop new strategies. It has been known that, in the process of evolution, a number of genes, theso-called xenogeneic homologous genes, are well-conserved and show the structural and/or functional similarity betweenvarious species to some degree. The nucleotide changes between various xenogeneic homologous genes are derived frommutation, and most of them are neutral mutations. Considering that the subtle differences in xenogeneic homologousgenes can break immune tolerance, enhance the immunogenicity and induce autologous immune response so as to elimi-nate tumor cells, we expect that a strategy of inducing autoimmune response using the property of xenogeneic homologousgenes will become a new therapy for cancer. Moreover, this therapy can also be used in the treatment of other diseases,such as autoimmune diseases and AIDS. This article will discuss the xenogeneic homologous genes, molecular evolutionand cancer therapy.     

Development of a nano-immunomodulator encapsulating R837 and caffeine for combined radio-/immunotherapy against orthotopic breast cancer

Immunotherapy is an ascendant approach in cancer treatment. It shows more pronounced effects on killing cancer cells in a specific manner in particular against metastasis more than traditional techniques, such as chemotherapy or surgery. However, tumor immunosuppression limits the response of the immune system to cancer development. In this study, we developed a lipid-based nanocarrier doubly loaded with imiquimod (R837), a toll-like receptor 7 agonist, and caffeine, an adenosine receptor antagonist. This R837/caffeine loaded nanocarrier served as a nano-immunomodulator (RC-nIM) for combination treatment with radiotherapy (RT) against orthotopic breast cancer. RT-induced immunogenic cell death facilitated the production of tumor antigen and elicited the immune response in corporation with R837-medaited activation of antigen-presenting cells (APCs) while RC-nIMs being adopted. Additionally, caffeine, an adenosine analog, can successfully compete with adenosine in the tumor. The tumor-bearing mice that received RT together with RC-nIMs experienced the best antitumor effects and exhibited higher levels of T cells and APCs within the tumor; the growth of secondary tumors was also limited. This work serves as a proof-of-concept study for the development of a new immunotherapy strategy against cancer.     

Prevention of HIV-2 and SIVsm infection by passive immunization in cynomolgus monkeys.

Infection of macaques with simian immunodeficiency virus (SIV) and human immunodeficiency virus type 2 (HIV-2) are useful models for studies of immunotherapy and vaccination against HIV as well as for testing of antiviral drugs. Vaccine research showing protective immunity in immunized monkeys has indicated that it will be possible to develop a vaccine for prevention of human HIV infection, although many hurdles remain. The design of an HIV vaccine would be helped if the basis of the protective immunity could be elucidated. Passive immune prophylaxis offers a means to determine the relative role of antibodies in protection against infection. We have studied whether a transfer of antibodies can prevent HIV-2 and SIVsm (SIV of sooty mangabey origin) infection in cynomolgus monkeys. Sera with high antibody titres were collected, heat-treated and injected into naive animals 6 h before challenge with 10-100 monkey-infectious doses of live homologous virus. All control animals treated with normal monkey serum (n = 6) or no serum (n = 39) became infected by the challenge virus, whereas five out of seven animals pretreated with antibody-containing serum at a dose of 9 ml kg-1 resisted infection. Thus passively transferred antibodies can protect against a low-dose lentivirus challenge in a nonhuman primate.     

1,25(OH)_2VD_3在过敏原特异性免疫治疗花粉过敏哮喘中的应用

以1,25(OH)₂VD₃为佐剂制备软叶针葵花粉变应原疫苗,以小鼠致敏哮喘模型为研究对象进行特异性免疫治疗.通过检测小鼠气道高反应性、血清中特异性抗体、细胞因子以及肺组织病理学切片等指标对治疗模型的构建进行评价,探讨1,25(OH)₂VD₃在过敏原特异性免疫治疗花粉过敏哮喘免疫机制中的作用.结果表明:以1,25(OH)₂VD₃为变应原疫苗能有效抑制花粉特异性IgE的产生和Th2细胞因子IL-4分泌,促进封闭性抗体IgG2a产生和Th1细胞因子IFN-γ的分泌,增加耐受性细胞因子IL-10生产,使Th2反应向Th1反应转变.1,25(OH)₂VD₃在花粉过敏性哮喘治疗中能大幅提高过敏原特异性免疫治疗的疗效.     

Prospects for a vaccine against the hepatitis C virus

The recent discovery of natural immunity to the hepatitis C virus and vaccine efficacy in the chimpanzee challenge model has allowed optimism about the development of at least a partly effective vaccine against this heterogeneous pathogen that is responsible for much of the chronic liver disease around the world. The immune systems of some infected individuals can spontaneously clear the virus, whereas other people need treatment with antivirals that work partly by stimulating humoral and cellular immune responses. Therefore, therapeutic vaccine strategies are also being pursued to improve treatment outcome.     

肿瘤免疫:肿瘤治疗的新希望

 随着肿瘤学、免疫学及分子生物学等相关学科的迅速发展和交叉渗透,肿瘤免疫治疗技术突飞猛进,成为肿瘤治疗新的热点。肿瘤免疫治疗是应用免疫学原理和方法,提高肿瘤细胞的免疫原性和对效应细胞杀伤的敏感性,激发和增强机体抗肿瘤免疫应答,并应用免疫细胞和效应分子输注宿主体内,协同机体免疫系统杀伤肿瘤、抑制肿瘤生长。在某些肿瘤,如黑色素瘤、非小细胞肺癌等,免疫治疗展现出强大的抗肿瘤活性,部分免疫治疗药物已经获得美国FDA批准。2013年《Science》杂志将肿瘤的免疫治疗评为年度最重要的科学突破。免疫治疗成为继手术、放射治疗和化学治疗之后又一种重要的抗肿瘤治疗手段,成为攻克恶性肿瘤的希望。本文综述肿瘤免疫学的历史、发展规律、未来方向及中国的肿瘤免疫发展情况。     

2018年肿瘤免疫研究热点回眸

 肿瘤免疫疗法已成为肿瘤治疗的重要手段，是肿瘤研究领域的焦点和热点。肿瘤免疫治疗相关药物相继问世，而2018年度诺贝尔生理学或医学奖授予两位在肿瘤免疫治疗中有突出贡献的免疫学家，更是确立了肿瘤免疫治疗时代的到来。本文概述了2018年肿瘤免疫治疗研究的热点及进展，包括新的肿瘤免疫检查点的发现、T细胞耗竭的深入探究、新的肿瘤免疫抑制细胞亚群的发现以及肿瘤免疫治疗新策略的探索。