转铁蛋白受体单抗WuT9导向治疗晚期肝癌

应用转铁蛋白受体单抗WuT9对晚期肝癌进行了临床研究，4例进行了放射免疫显像检查，22例进行了临床治疗观察。结果表明：（1）4例显像检查病人中，有3例肿瘤于注射^131I-WuT9偶联物后第7天呈清楚显像；（2）22例接受阿霉素－WuT9偶联物治疗后，近期疗效观察：18例有效，7例显效，远期随访2年者15例，4例存活，其中2例存活已4年；对照组10例，有效仅3例，无显效，无1例存活2年。     

阿霉素与转铁蛋白受体单抗偶联方法探讨：以葡聚糖DextranT10 …

以７５％，５０％，３０％和２５％氧化程度的葡聚糖为偶联剂，制备阿霉素与转铁蛋白受体单抗的偶联物Ｃ７５，Ｃ５０，Ｃ３０和Ｃ２５，并对其各方面参数作了比较，结果表明，其偶联度分别为１６２，１０３，７２与５２Ｍｏｌｅｓ／每个抗体分子，即葡聚糖的氧化程度越高，其偶联度越高，然而，在１３１１－ＳｐＡ为二抗的细胞结构分析结果表明，Ｃ７５，Ｃ５０均丧失大部分的抗体活性，３Ｈ－ＴｄＲ掺入细胞制实验也表明，Ｃ７５与     

转铁蛋白、转铁蛋白受体与肝脏

转铁蛋白、转铁蛋白受体与肝脏生理、病理及临床有密切关系。肝脏是合成、分解转铁蛋白的主要器官。转铁蛋白的检测是估价肝脏功能、早期诊断酒精中毒和血色病的有效指标。肝脏含有较丰富的转铁蛋白受体,遗传性血色病时受体减少,肝细胞再生、肝细胞恶性变时转铁蛋白受体增加。检测转铁蛋白受体对肝癌的早期诊断和鉴别诊断有一定价值,提示核素标记的转铁蛋白、抗转铁蛋白受体的抗体可作肝癌放射免疫定位和生物导向治疗。     

肝细胞癌转铁蛋白受体表达的免疫电镜研究

用转铁蛋白受体（ＴＦＲ）单抗ＯＫＴ５，以免疫电镜技术，对肝细胞癌（ＨＣＣ）ＴＦＲ的表达作亚细胞定位研究，结果表明，ＴＦＲ电镜下呈电子密度较高的颗粒状物质，肝癌细胞大量表达，正常肝细胞不表达或少量表达，肝癌细胞的ＴＦＲ分布在细胞，但更多地分布的胞浆，从而证实先前定位与定量的研究结果，并根据ＴＦＲ所在位置，就其在细胞的动态过程作了探讨。     

雄激素受体与原发性肝细胞癌

现已明确,正常人肝细胞中存在低浓度、高亲和力的雄激素受体。肝细胞癌时肝脏雄激素受体的表达可增加。作为一种介导物,雄激素受体参与肝细胞癌的发生和发展。但其确切机制有待于进一步阐明。部分肝细胞癌为雄激素依赖性,基于此特点,可望对肝细胞癌开展内分泌治疗。     

抗体偶联药物应用于乳腺癌治疗的研究进展

［摘要］　抗体偶联药物（ADC）是一种很有潜力的新型靶向药物,具有抗体选择性强和药物活性高的优势。近年来,通过选择不同的靶点和小分子毒性物质,再加上连接方式的改进,有效的新型抗体偶联药物不断研发上市,代表着个体化精准治疗的快速发展。目前,全球范围内已有3种抗体偶联药物获批治疗乳腺癌,除用于人表皮生长因子受体2（HER2）阳性乳腺癌的曲妥珠单抗-美坦新偶联物（T-DM1）和曲妥珠单抗-德鲁替康（T-DXd,DS-8201）外,还有可使三阴性乳腺癌（TNBC）获益的戈沙妥珠单抗（SG,IMMU-132）。该文就近年来抗体偶联药物应用于乳腺癌治疗的国内外研究作一综述。     

转铁蛋白受体单克隆抗体偶联物与碘油混悬剂联合肝动脉栓塞治疗中晚期肝癌

转铁蛋白受体单克隆抗体偶联物与碘油混悬剂联合肝动脉栓塞治疗中晚期肝癌广东省惠州市中心人民医院（５１６００１）凌红肖铣德许岸高黄尧生经皮股动脉穿刺肝动脉栓塞术被认为是不宜手术的肝癌病人的重要治疗方法。但因单纯栓塞疗效不完全，常需综合治疗。联合使用转铁蛋...     

抗人甲胎蛋白单克隆抗体的研究和应用

目前抗人甲胎蛋白单克隆抗体(AFP McAb)杂交瘤细胞均属鼠-鼠系统,主要应用于肝细胞癌和胚胎性肿瘤的诊断、良性肝瘤与肝脏恶性肿瘤的鉴别诊断、肝细胞癌的导向治疗等方面。血清学诊断结果显示单抗明显优于多抗,不仅敏感而且特异性强,可检出血清AFP 的最低浓度为2.2ng/ml。AFP McAb 核素标记后体内定位诊断肝细胞癌的动物实验已获成功。有关AFP McAb 导向治疗的临床应用尚未见报道,但不乏动物试验成功的实例。抗人AFP McAb 临床应用于肝癌的诊断和治疗的前景是广阔的。     

接受纳武单抗治疗的晚期肝细胞癌患者炎症生物标志物与临床转归的相关性

正【据Journal of Hepatology 2020年7月报道】题:接受纳武单抗治疗的晚期肝细胞癌患者炎症生物标志物与临床转归的相关性(作者Sangro B等)程序性死亡因子-1(PD-1)抑制剂纳武单抗治疗晚期肝细胞癌患者具有持久的疗效,较高的安全性,且能够显著提高患者的生存期。该研究回顾性分析了接受纳武单抗治疗的肝细胞癌患者的免疫生物学特征以及生物标志物和临床转归之间可能的相关性。     

受体导向抗病毒药物导向性的实验研究

本文以乳糖化人血清白蛋白作为载体，与抗病毒药物单磷酸阿糖腺苷交联成导向抗病毒治疗药物(下称交联物)，研究其对肝脏的导向性能。用同位素标记示踪实验显示．交联物在肝脏内含量明显高于其它脏器(P<0．001)；胶体金银染色法显示，受体定位于肝细胞血窦面及其侧面，交联物内化实验研究显示，其内化过程及动力学变化符合导向治疗要求。本研究为抗肝炎病毒导向治疗的临床应用提供了实验依据。     

Effects of idiotypic human anti-mouse antibody against in vitro binding and antitumor activity of a monoclonal antibody-drug conjugate

BACKGROUND/AIMS: Because the HAMA (human anti-mouse antibody) response following administration of murine monoclonal antibodies represents mainly isotypic HAMA production, idiotypic HAMA responses have not been thoroughly analyzed. METHODOLOGY: In the present study we examined the effect of idiotypic HAMA that arose in patients who had repeatedly received murine monoclonal antibody conjugated to an anticancer drug against in vitro binding and antitumor activity of the conjugate. HAMA that had developed after administration of tumor-specific murine monoclonal antibody A7 conjugated with neocarzinostatin were measured in patient serum. The inhibitory effect of HAMA on tumor binding and antitumor activity of the A7-neocarzinostatin conjugate was examined in cultures of human colonic carcinoma cells. RESULTS: The serum concentration of idiotypic HAMA in patients administered A7-neocarzinostatin was significantly higher than that in a control group. Binding activity and antitumor activity of A7-neocarzinostatin against target cells was reduced in the presence of sera containing HAMA. CONCLUSIONS: Repeated use of A7-neocarzinostatin can be expected to show less antitumor effect than the first use of the conjugate.     

Natural killer cell activity in patients with liver cirrhosis relative to severity of liver damage

To evaluate the role of severe liver damage on natural killer cell activity, 29 patients with liver cirrhosis were examined. The natural killer cell activity was measured with a 4-hr chromium release assay, and the K562 cell line was employed as target cells. The natural killer cell activity was significantly decreased in cirrhotic patients compared with normal controls and patients with chronic active hepatitis. Cirrhotic patients with Pugh's C grade of severity of liver disease had lower natural killer cell activity. The depression of natural killer cell activity in cirrhotic patients was inversely correlated with prothrombin time ratios, and the natural killer cell activity in cirrhotic patients with hepatic encephalopathy was lower than in patients without hepatic encephalopathy. Thus, the diminished natural killer cell activity in cirrhotic patients might be related to the severity of liver damage.     

药物标记抗体导向治疗老年人免疫性血小板减少性紫癜的实验研究

目的 探讨药物标记抗体导向治疗老年人免疫性血小板减少性紫癜的可行性及效果。方法 分别用间接和直接交联法交效注射用免疫球蛋白（ＩＶＩＧ）与氨甲喋吟是备成标记抗全,用间接免疫荧光法检测标记抗体Ｆｅ段结合活性,以Ｆｃ受体阳性的小鼠巨噬细胞和人单核细胞白血病细胞株Ｕ９３７为靶细胞,用ＭＴＴ法测定标记抗体的杀伤活性。结果 标记抗体对巨噬细胞的杀伤作用明显大于游离ＭＴＸ;标记抗体对Ｆｃ受体阳性细胞的杀伤作用明     

Killer cell activity of human monoblastic leukemia cells as detected with a monocyte-specific target cell

Peripheral blood leukemia cells from patients with acute monoblastic leukemia (AMoL) were tested for killer cell activity against target cells that detected natural killer cell-mediated or monocyte-mediated spontaneous cytotoxicity. The fibrosarcoma cell line Wehi 164, pretreated with actinomycin D to induce susceptibility to lysis, specifically detects the activity of unstimulated human monocytes. In four of six cases of AMoL, high killer cell activity could be measured against this target. In three of these four cases, the killer cell activity could be assigned exclusively to the leukemic clone, based on the high leukocyte counts and the resultant dilution of normal cells, as evidenced by marker and by functional analysis. While leukemic cells with killer cell activity against Wehi 164 contained 34% to 45% cells that were positive for binding of the 63D3 monoclonal antibody, the two leukemic samples without killer cell activity contained only 1% and 12% 63D3-positive cells. Cell sorting of 63D3-positive and -negative cells from two leukemias with killer cell activity demonstrated that the killer cell activity was restricted to the 63D3-positive fraction of AMoL cells. These data demonstrate that monoblastic leukemia cells can be potent killer cells and that killing activity is linked to the 63D3- defined cell surface molecule.     

Functional character and augmentation of lymphocytes in regional lymph nodes of patients with lung cancer

It appears that lymph node metastases are more frequent in lung cancer than in other cancers because of impaired defensive mechanisms in the regional lymph nodes. However, little is known about the immunologic function of regional lymph node lymphocytes (RLNL) in patients with lung cancer. We have studied the immunologic properties of RLNL in comparison with peripheral blood lymphocytes (PBL). We measured the natural killer (NK) cell activity of RLNL and PBL in patients with lung cancer and found that the NK activity was significantly more depressed in the RLNL than in the PBL. In contrast, interleukin-2 (IL-2) production was markedly higher in the RLNL than in the PBL. The cytotoxic effect of RLNL in nonmetastatic lymph nodes on target cells (such as K562 cells) or PC-3 and PC-10 cells (NK-resistant, human lung cancer of adenocarcinoma and epidermoid carcinoma, respectively) was significantly enhanced by in vitro incubation with recombinant IL-2 (rIL-2). Furthermore, we clarified that both rIL-2 and OK-432, which is a biologic response modifier and IL-2 inducer as well, augmented the cytotoxicity of RLNL and that these effector cells were lymphokine-activated killer (LAK) cells. The depletion of lymphocyte subsets by pretreatment with specific monoclonal antibody showed that the LAK activity in RLNL was mediated by CD3+ and CD8+ cells, whereas the lymphocyte subsets contributing the LAK activity in PBL were CD3+ and CD16+ cells. It was concluded that a majority of the effector cells in RLNL were LAK cells of the cytotoxic T cell population.     

Immunological studies before and during interferon therapy in chronic HBV infection: identification of factors predicting response.

Lymphoblastoid interferon is effective therapy in some but not all patients with chronic hepatitis B virus infection. To assess whether immunological parameters were predictive of response to interferon therapy, we determined the human leukocyte antigen type, CD4/CD8 ratio, natural killer cell activity, IgM anti-HBc antibody levels and concanavalin A-induced lymphocyte proliferative response in 30 patients before treatment. In addition, to investigate the mechanisms of action of interferon in promoting hepatitis B virus clearance, we serially measured the CD4/CD8 ratios, natural killer activity and lymphocyte proliferative response at wk 4, 8 and 12 of treatment. A beneficial response to therapy was defined as the sustained clearance of HBeAg and serum hepatitis B virus DNA within 1 yr of commencing therapy. Elevated IgM anti-HBc levels were associated with a beneficial response to therapy, but there was no correlation observed between response and pretreatment CD4/CD8 ratio, natural killer activity or lymphocyte proliferative response. Six of seven human leukocyte antigen DR3-positive patients responded. No measurable changes in the immunological parameters studied were observed in the nonresponder group, whereas a significant rise in CD4/CD8 ratio, associated with a fall in peripheral CD8 number and a decline in measurable NK activity, was seen in the responder group. These changes were maximal at the time of hepatitis B virus DNA clearance, which was associated with a transient increase in hepatic inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human mucosal cytotoxic effector cells

Human intestinal lamina propria mononuclear cells have been shown to mediate mitogen-induced cellular cytotoxicity, antibody-dependent cellular cytotoxicity, and lymphokine activated killer cell function. However, although natural killer cells have been demonstrated in the gut mucosa of rodents, recent reports found little or no spontaneous cytotoxic activity in the lamina propria of the human gut. Using the natural killer cell-related monoclonal antibody NKH-1, which has not previously been applied to studies of mucosal killer cell function, we have shown by immunofluorescence that 2%-3% of enzymatically dispersed lamina propria lymphocytes are NKH-1+. A "panning" technique was then used to enrich for the NKH-1+ cells. Panned cells were consistently greater than or equal to 80% NKH-1+ by indirect immunofluorescence. Unlike their counterparts in the peripheral blood, the mucosal NKH-1+ cells were Leu-11-. Although unseparated lamina propria lymphocytes failed to exhibit natural killer activity against K562 targets in 4-h chromium release assays at effector to target ratios of up to 100:1, the NKH-1+ cells were cytolytically active at ratios of less than 5:1. Mucosal lymphocytes depleted of natural killer cells (NKH-1-) exhibited cytotoxic activity when cultured for 72 h with interleukin-2. The precursors of the lymphokine culture activated phenomenon were NKH-1-, Leu-11-, T4-, T3-, T11+, and T8+. Although lamina propria T3+ cells did not exhibit spontaneous or culture activated cytotoxicity, they were shown to exhibit nonspecific anti-CD3 (anti-T3)-induced T-cell cytotoxicity. In conclusion, functional natural killer and lymphokine activated killer cells are both present in the human gut mucosa and represent distinct populations of cytotoxic cells. In addition, anti-CD3-induced cytotoxicity is a feature of mucosal T cells. These mucosal killer cell subsets differ phenotypically from those previously described in the peripheral blood.     

Natural Killer Cells—A New Cytotoxic Mechanism Against Tumours?

Summary: Natural killer cells–a new cytotoxic mechanism against tumours? P. Hersey, Aust. N.Z. J. Med., 1979, 9, pp. 464–472. Lymphoid cells from the blood of most normal human subjects can kill a variety of cultured tumour cells in vitro. The cytotoxic activity of these cells (now referred to as natural killer cells) was initially detected during studies on known cytotoxic cells such as T cells, antibody dependent effector (K) cells and macrophages and was regarded as having no biological importance. Studies over the past few years have suggested, however, that natural killer cells may represent a major surveillance mechanism against tumours in vivo and may be the only cytotoxic mechanism against many tumours when those based on antigen recognition by the “conventional immune” cells fail. The nature of these cells and their cytotoxic mechanism has received considerable attention, but has so far not been clearly defined. A considerable body of evidence suggests they are of the T cell lineage but if so they are a sub-population of T cells that develop independently of the thymus. Recent studies suggest that interferon may play a major role in the induction of natural killer activity and this finding promises to be an important advance in our understanding of this cytotoxic mechanism. The level of natural killer cell activity against tumours in both animals and humans appears to be genetically determined and may be linked to genes of the major histocompatibility complex. Evidence for the biological importance of these cells was suggested by experimental studies where the in vivo susceptibility of animals to tumour growth could be related to the levels of their natural killer cell activity. Conversely, the take of different tumour cells in animals was inversely related to their susceptibility to natural killer cells. Studies on transplantation of bone marrow in animals also indicated that natural killer cell activity may be the predominant mechanism responsible for rejection of these grafts. Studies of a similar nature in humans are as yet limited but initial results from those on melanoma patients support the view that these cells are also important against tumours in human subjects. No information is yet available as to their importance in rejection of bone marrow grafts in human recipients. NK cells are therefore the latest of the effector cells to be defined after T cells, 6 cells, macrophages and K cells. These studies suggest that measurement of the activity of these cells warrants further attention in patients with tumours and bone marrow transplants and that methods to alter their activity may assume an important role in therapeutic procedures against tumours or in transplantation of bone marrow.     

病毒感染对慢性阻塞性肺病患者免疫功能的影响

为探讨病毒感染对慢性阻塞性肺病（COPD）患者免疫功能的影响，检测了64例COPD急性发作期患者的呼吸道病毒特异抗体IgG、IgM，自然杀伤细胞活性（NK－A），T淋巴细胞亚群及体液免疫IgA、IgG、IgM。结果显示，COPD急性发作期呼吸道合胞病毒（RSV）、腺病毒（ADV)、柯萨奇病毒（COX）、巨细胞病毒（CMV）特异抗体IgG、IgM的阳性率分别是45％、25％，22％、28％及11％、5％和3％、5％。病毒抗体阳性组NK－A和T淋巴细胞亚群显著低于病毒抗体阴性组，而体液免疫无显著差异。提示病毒感染对COPD患者的细胞免疫有明显抑制作用，可能是COPD反复发作的原因之一。     

Natural killer cell depletion and diabetes mellitus in the BB/Wor rat (revisited)

Summary The BB/Wor diabetes-prone rat is an animal model of human insulin-dependent diabetes mellitus. In this model of spontaneous autoimmunity, natural killer cells are candidate cytotoxic effector cells, believed to be the mediators of beta-cell cytolysis in vivo. We therefore studied the effects of an anti-natural killer cell monoclonal antibody on the spontaneous development of diabetes in the BB/Wor rat. The 3.2.3 monoclonal antibody recognizes a molecule present on rat natural killer cells and selectively depletes these cells in vivo. Chronic treatment of diabetic-prone rats with 3.2.3 monoclonal antibody cleared circulating phenotypic natural killer cells, depleted in vitro spleen natural killer cell function, and profoundly reduced intra-islet accumulation of 3.2.3⁺ cells, but did not prevent or delay the onset of diabetes. These results indicate that natural killer cells are not necessary for the development of spontaneous diabetes in BB/Wor rats.