T淋巴细胞相关肿瘤免疫疗法的研究进展

目的:了解T淋巴细胞相关肿瘤免疫疗法的研究进展,以期为肿瘤的免疫治疗提供参考。方法:笔者查阅近年来国内外相关文献,就T淋巴细胞相关肿瘤免疫疗法的研究进行归纳和总结。结果:T淋巴细胞相关肿瘤免疫疗法免疫检查点疗法和嵌合抗原受体T细胞免疫疗法在临床前与临床研究中取得了良好的成效。多个肿瘤免疫治疗药物,尤其是针对细胞毒T淋巴细胞相关抗原4、程序性死亡受体1(PD-1)和PD-1配体这3个靶标的肿瘤免疫治疗药物被各研究机构和医药企业作为研发热点,其中Ipilimumab、Tremelimumab和Nivolumab已被FDA批准用于临床,且疗效显著。肿瘤免疫疗法通过诱导自身免疫系统对抗肿瘤,但多种因素影响T淋巴细胞对肿瘤的识别,造成肿瘤免疫逃逸。结论:肿瘤免疫疗法还存在一定的局限性,但其在肿瘤治疗中是一个非常有前景的研究方向,有望成为攻破肿瘤治疗的有效方法。     

嵌合抗原受体T细胞免疫疗法治疗多发性骨髓瘤的研究进展

免疫疗法在恶性肿瘤治疗中的应用正日益受到关注.嵌合抗原受体(CAR)技术是一种新兴的免疫疗法,在血液肿瘤的治疗上具有巨大的潜力.嵌合抗原受体T细胞免疫疗法(CAR-T)可通过特异性识别靶抗原来杀伤骨髓瘤细胞,使治疗复发难治性多发性骨髓瘤成为可能.该文重点对CAR-T在多发性骨髓瘤治疗方面的研究进展作一综述,并对可能作为CAR-T治疗多发性骨髓瘤的靶抗原进行了分析.     

嵌合抗原受体T细胞治疗恶性肿瘤的研究进展

以嵌合抗原受体为基础的细胞免疫治疗已成为治疗恶性肿瘤的一种新策略。其主要特点是通过基因修饰获得携带识别肿瘤抗原特异性受体T细胞并赋予T细胞靶向杀伤活性的个性化治疗方法。与传统的T细胞免疫疗法相比,嵌合抗原受体可以通过增加共刺激分子信号从而增强T细胞抗肿瘤的杀伤性,并可克服肿瘤局部免疫抑制微环境和打破宿主免疫耐受状态,随着转化医学研究的不断深入,基于嵌合抗原受体的免疫治疗新策略会给肿瘤患者带来新的希望。     

肿瘤免疫治疗中过继性细胞疗法的研究进展

肿瘤免疫疗法旨在利用免疫系统建立针对性的抗肿瘤免疫反应,激活肿瘤免疫细胞是免疫疗法的关键点.过继性细胞疗法是通过体外改造、扩增免疫细胞提高免疫功能,再回输患者体内以发挥抗肿瘤效应.除了已广泛应用于临床的嵌合抗原受体T细胞疗法,近年来T细胞受体-T细胞疗法、肿瘤浸润淋巴细胞疗法、嵌合抗原受体-自然杀伤细胞疗法、嵌合抗原受...     

凋亡抑制蛋白家族与肿瘤治疗的研究进展

1前言　　目前认为肿瘤治疗失败的主要原因是癌细胞对化疗、放疗及细胞毒T细胞和自然杀伤细胞介导的免疫疗法不敏感,事实上,这些看似不同的治疗方法是通过相同的生物学的机制即细胞凋亡的方式来消除肿瘤的.     

肺癌的过继免疫疗法的临床应用研究

所谓过继免疫疗法是通过将肿瘤致敏T淋巴细胞移入患癌宿主体内,而得到抗肿瘤效果的方法,这个方法对于进行性增殖着的肿瘤治疗上很有效,肿瘤的消失及免疫状态的获得在许多动物实验上得已证实。过继免疫疗法的临床应用。一、对于NSCLC病例术后过继免疫疗法。 (一)对象:NSCLC手术病例术后病期ⅡⅢA;     

新药物使1/4患者肿瘤变小

<正>一类新药抑制了肿瘤细胞对抗T细胞的"盾",从而使其能够遭受攻击。一种有助于人体免疫系统攻击肿瘤的药物正在崭露头角。在有几百名各类晚期癌症患者参与的早期临床试验中,多达1/4接受治疗的人出现了肿瘤收缩,并且有的人至今依然活着。这些结果是所谓免疫疗法的最新好消息,这种疗法试图通过克服肿瘤逃避     

肿瘤的免疫治疗：改变平衡

肿瘤抗原反应性淋巴细胞过继性免疫治疗（ACT）是肿瘤免疫疗法中最有前景的策略之一，即在体内注入在体外激活的自体肿瘤反应性T细胞。ACT的作用已经在黑素瘤的治疗中得到验证，与非清髓性造血干细胞移植治疗联合应用，减少了宿主淋巴细胞数目且使肿瘤特异性CD8^＋T细胞增多。     

水凝胶在肿瘤免疫治疗中的研究进展

近年来,免疫疗法在癌症治疗领域受到了极大的关注,联合治疗已经产生了良好的临床治疗效果。然而,患者对免疫治疗的反应率仍然不高,这需要注意肿瘤部位的药物利用率和全身性副作用。水凝胶作为载药平台具有极大的优点,可将抗肿瘤药物直接递送至肿瘤部位,降低全身毒性,并具有良好的可降解性。本篇综述报道了基于水凝胶平台的药物输送系统的新进展,包括免疫化学治疗、免疫放疗和免疫光热治疗等多种免疫治疗联合治疗。     

肿瘤免疫学研究的一些进展

肿瘤免疫学的研究只有十余年的历史,但进展非常迅速。近年来,不仅在肿瘤免疫机制方面提出了一系列的论述,而且已经开辟了免疫诊断与免疫疗法这样崭新的概念,并应用于临床。免疫疗法已被认为是治疗肿瘤的第四手段,即在传统治疗肿瘤三大手     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

---

Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.