Disulfide-stabilized single-chain antibody-targeted superantigen: Construction of a prokaryotic expression system and its functional analysis

AIM: To construct the expression vector of B3 (scdsFv)-SEA (D227A) and to identify its binding and cytotoxic ability to B3 antigen positive carcinoma cell lines.METHODS: This fusion protein was produced by a bacterial expression system in this study. It was expressed mainly in the inclusion body. The gene product was solubilized by guanidine hydrochloride, refolded by conventional dilution method, and purified using SP-sepharose cation chromatography.RESULTS: The expression vector B3 (scdsFv)-SEA-PETwas constructed, the expression product existed mainly in the inclusion body, the refolding product retained the binding ability of the single-chain antibody and had cytotoxic effect on HT-29 colon carcinoma cells. The stability assay showed that the resulting protein was stable at 37 ℃.CONCLUSION: This genetically engineered B3 (scdsFv)-SEA fusion protein has bifunction of tumor targeting and tumor cell killing and shows its promises as an effective reagent for tumor-targeted immunotherapy.

Cyclosporin A protects Balb/c mice from liver damage induced by superantigen SEB and D-GaIN

AIM To investigate the pathogenic effect ofSEB and D-GalN on liver and the protection ofcyclosporin A, the relationship between hepaticapoptosis and necrosis and the possiblemechanism of acute hepatic necrosis.METHODS After staphylococcal enterotoxin B(SEB ) mixed with D--galactosamine (D-GaiN )were injected intraperitoneally into Balb/c miceand those previously treated with cyclosporin A,blood samples were collected and livers wereisolated at 2, 6, 12 and 24 h. Patterns othepatocellular death were studiedmorphologically and biochemically, circulatingcytokines (TNF-a, IFN--y ) and mice mortalitywithin 24h was assessed.RESU’LTS The SEB could induce the typicalapoptotic changes of hepatocytes, the D-GaiNcould induce hepatocytes apoptosis anddegeneration at the same time, and the micehaving received the SEB + D-GaiN injectionsdeveloped apoptosis at 2 and 6 h, but after 12 hhepatocytes were characterized by severein jury, whereas all the examinations in thecyclosporin A treated mice were normal.CONCLUSION Hepatic cell apoptosis might berelated to necrosis, and massive hepatocyteapoptosis is likely the initiating step of acutehepatic necrosis in mice. The effects induced bySEB and D--GaiN on hepatocytes might bemediated by T cells, and could be prevented bycyclosporin A.

Update on molecular diversity and multipathogenicity of staphylococcal superantigen toxins

Staphylococcal superantigen(SAg)toxins are the most notable virulence factors associated with Staphylococcus aureus,which is a pathogen associated with serious community and hospital acquired infections in humans and various diseases in animals.Recently,SAg toxins have become a superfamily with 29 types,including staphylococcal enterotoxins(SEs)with emetic activity,SE-like toxins(SEIs)that do not induce emesis in primate models or have yet not been tested,and toxic shock syndrome toxin-1(TSST-1).SEs and SEIs can be subdivided into classical types(SEA to SEE)and novel types(SEG to SEIY,SE01,SE02,SEI26 and SEI27).The genes of SAg toxins are located in diverse accessory genetic elements and share certain structural and biological properties.SAg toxins are heat-stable proteins that exhibit pyrogenicity,superantigenicity and capacity to induce lethal hypersensitivity to endotoxin in humans and animals.They have multiple pathogenicities that can interfere with normal immune function of host,increase the chances of survival and transmission of pathogenic baaeria in host,consequently contribute to the occurrence and development of various infeaions,persistent infeaions or food poisoning.This review focuses on the following aspeas of SAg toxins:(1)superfamily members of classic and novelty discovered staphylococcal SAgs;⑵diversity of gene locations and molecular structural characteristics;(3)biological characteristics and activities;(4)multi-pathogenicity of SAgs in animal and human diseases,including bovine mastitis,swine sepsis,abscesses and skin edema in pig,arthritis and septicemia in poultry,and nosocomial infections and food-borne diseases in humans.

THE EFFECT OF SUPERANTIGEN STAPHYLOCOCCALENTEROTOXIN B AND D-GALACTOSAMINE ON BALB/CMOUSE HEPATOCYTES

Objective To observe the role of superantigen staphylococcal enterotoxin B(SEB) andD - galactosamine (D - GalN) on Balb/c mouse hepatocytes and its mechanism. Methods After Balb/c mice wereinjected intraperitoneally with SEB, D- GalN or both, blood samples were collected and livers were removed at 2,6, 12, 24h. Patterns of hepatocellular death were studied morphologically and biochemically, circulating cytokines(TNF, IFN-γ) were determined, and mice mortality within 24h was assessed. Results SEB could induce thetypical apoptotic changes of hepatocytes morphologically and biochemically. The mechanism is probably associatedwith the production and release of Cytokines (such as TNF, IFN- γ, etc).D - GalN could induce hepatocytesapoptosis and degeneration at the same time. Besides this, we confirmed hepatocytes of the mice which wereadministered SEB and D - GalN developing apoptosis at 2, 6h, but after 12h hepatocytes were characterized bysevere injury, the mice mortality within 24h is 50%. Conclusion SEB or D - GalN alone could induce the typicalapoptotic changes of hepatocytes. SEB+D-GalN developed hepatocytes apoptosis in the early stage and necrosisin the later. It suggests that there is some relationship between hepatic cell apoptosis and necrosis, and massivehepatocyte apoptosis is the probably initiating step of acute hepatic necrosis in mice.

Effect and Mechanism of Superantigen Staphylococcal Enterotoxin Therapy for Mouse Gastric Tumor

The anti-tumor effect and mechanism of the staphylococcal enterotoxin A (SEA) were studied. The mouse gastric tumor model was produced by subcutaneously inoculating gastric tumor ceils (MGC80-3). The experimental group was treated with SEA, and the control group was treated with normal saline. The percentage of tumor generation and tumor mass was measured. The results showed that the percentage of the tumor generation in the SEA-treated mice was lower than in the control group, but there was no significant difference (P>0. 05). However, the tumor mass in the experimental group was significantly lighter than in the control group, with the difference being very significant (P<0. 001). There were more CD4+ T cells and CD8+ T cells in the tumor of the mice treated with SEA than those of the control group. SEA has an obvious anti-tumor effect on mice gastric tumor. The mechanism might be that SEA induces the effect of superantigen-dependent cell mediated cytotoxicity to the tumor cells.

Colonization by Superantigen Producing Staphylococcus aureus in Mice Enhances the Capacity to Develop Oral Tolerance

Microbial stimulation in early childhood may be necessary for proper maturation of the immune system. Infants colonized with Staphylococcus aureus have low risk of developing food allergy. Neonatal exposure to staphylococcal superantigen improves oral tolerance and enhances protection in experimental allergy models. Here, we used three wild-type strains of S. aureus, naturally harboring genes for different superantigens (SElM/SElO alone, or in combination with SEA or TSST-1). We first investigated their in vitro stimulatory capacity of splenocytes from germ-free mice. Secondly, germ-free mice were colonized with the strains and their capacity to develop oral tolerance was tested in a food allergy model. In vitro, S. aureus with only SElM/SElO genes promoted the strongest B-cell stimulation. S. aureus carrying gene for SEA induced the highest proportion of CD4+FoxP3+ T cells. The proportion of regulatory T cells was inversely correlated to B-cell proliferation, indicating suppressive ability of these cells. All strains were equally able to colonize the germ-free gut, initially achieving 1010CFU/g faeces, which decreased to 105 over a period of six weeks. Mice colonized with S. aureus carrying genes for SEA or TSST-1 had improved capacity to develop tolerance compared to germ-free mice. These results suggest that colonization by S. aureus producing superantigens may improve active tolerance to gut allergens.

Linkage between PTK Signaling Pathway “Crosstalking” and Caspase-3/CPP32-like Proteases Activation in Signaling Transduction of CD4^+ T Lymphocytes Apoptosis Induced by Superantigen SEB

Exposure of naive murine CD4 + T lymphocytes to superantigen such as staphylococcal enterotoxin B (SEB) induces a strong proliferative response. Prolonged exposure or subsequent restimulation of the responding T cell population with SEB leads to the apoptotic events of activation-induced cell death (AICD). The signaling mechanism responsible for the AICD is a target of intensive investigation. However, the precise downstream signaling pathways of SEB-induced AICD remains unclear. Our results here show that the sequential activation of caspase-1/ICE-like and caspase-3/CPP32-like cysteine proteases probably plays a role in the signaling transduction of SEB-induced AICD, but caspase-3/CPP32-like proteases activation does not depend on caspase-1-like proteases activation. Herbimycin A, a specific inhibitor of protein tyrosine kinases, inhibit caspase-3/CPP32-like cysteine proteases activation. However, it does not prevent DNA fragmentation of CD4 + T cells apoptosis induced by SEB. These results indicate that protein tyrosine kinases pathway is probably involved in the signaling transduction of CD4 + T cells apoptosis induced by SEB and “crosstalks” with the pathway of caspase-3/CPP32-like proteases activation.

COMPARISON OF ASSISTANT EFFECTS AMONG ASSISTANT MOLECULES ON T CELL ACTIVATION BY SUPERANTIGEN TSST-1

对抗ＣＤ２８抗体、佛波酯（ＰＭＡ）和ＩＬ－２三种辅助分子在体外缺乏抗原提呈细胞（ＡＰＣ）的情况下辅助超抗原活化Ｔ细胞的作用进行比较。结果发现：抗ＣＤ２８抗体、ＰＭＡ和ＩＬ－２辅助超抗原活化Ｔ细胞的最适浓度分别为１０μｇ／ｍｌ、１０ｎｇ／ｍｌ和１０００ｕ／ｍｌ；其中，抗ＣＤ２８抗体辅助超抗原活化Ｔ细胞的作用最强，ＰＭＡ次之，ＩＬ－２最弱。另外，对三种辅助分子辅助超抗原活化Ｔ细胞的机制进行了探讨。本研究为今后选择合适的辅助分子与合成肽技术共同组建一种有效的探找超抗原Ｔ细胞表位的方法奠定了基础。

ANALYSIS OF MOTIF IN TCR Vβ HV4 SEQUENCES BINDING SUPERANTIGEN TSST-1

首先对４１种人和小鼠的Ｔ细胞受体β链可变基因编码肽段（Ｖβ）的氨基酸序列进行多序列对准，就Ｖβ之第四高变区（ＨＶ４）片段进行比较，分析与超抗原毒素休克综合征毒素－１（ＴＳＳＴ－１）结合的四种Ｖβ（小鼠Ｖβ３、Ｖβ１５、Ｖβ１７和人Ｖβ２）之ＨＶ４序列内是否存在特定的氨基酸残基排列模式。结果发现：小鼠Ｖβ３和Ｖβ１７的ＨＶ４具有特异的ＲＦＳＡＸＣＸＳＮＳ模式，而小鼠Ｖβ１５和人Ｖβ２的ＨＶ４则含独特的ＫＦＸＩＸＨ模式。提示：与ＴＳＳＴ－１结合的四种Ｖβ所对应的Ｔ细胞识别表位可能不止一个。

ACTIVATION OF TCELLS BY SYNTHETIC PEPTIDES OF SUPERANTIGEN TSST-1 UNDER ASSISTANCE OF ASSITANT MOLECULES

根据以往对超抗原ＴＳＳＴ－１分子的Ｔ细胞表位预测结果，从ＴＳＳＴ－１分子中选择了一段序列，合成了两个交叠肽，Ｔ３４和Ｔ５８；观察它们在辅助分子辅助下的促Ｔ细胞增殖能力。结果发现：Ｔ３４和Ｔ５８单独虽均不能活化人的ＰＢＭＣ或小鼠脾细胞，但在ＣＤ２８的共刺激或ＰＭＡ的辅助下却可活化人的ＰＢＭＣ和小鼠的脾细胞。提示：Ｔ３４和Ｔ５８不具备ＭＨＣ结合位，但含有Ｔ细胞表位，两者的Ｔ细胞表位可能位于两肽的共同序列内，即ＴＳＳＴ－１（１２５～１５８）。

Effect of superantigen on ion electrophysiology and permeability in rabbit maxillary sinus epithelia

Obejctive Superantigens are potent inflammatory stimuli which derive from pathogenic microbes such as bacteria, viruses and protozoa The aim of this study was to investigate the role of superantigens on the function of rabbit maxillary sinus epithelium Methods Twenty New Zealand white rabbits were divided into 4 groups Rabbit sinus mucosa was separated under a surgical microscope and mounted in Ussing chambers to record short circuit current, conductance and permeability to horseradish peroxidase (HRP) Group A was used as normal control Group B was stimulated with an injection of superantigen into the sinus for 4 hours The sinus mucosa of Group C was stimulated by the addition of tumor necrosis factor α (TNF α) into Ussing chambers Group D sinus mucosa was stimulated by superantigen after pretreatment with anti TNF α antibody Results Superantigen evoked increases in sinus epithelial cell baseline short circuit current, conductance and permeability to HRP stimulated by the addition of TNF α into Ussing chambers These were similar to results from superantigen stimulation in vivo The effect of superantigen on sinus epithelial cells could be blocked by pretreatment with anti TNF α antibody Conclusions Superantigen affected the function of sinus epithelial cells, including the capability of epithelial defensive barrier, which might be mediated by TNF α

沙棘果油对超抗原诱导的特应性皮炎小鼠激素抵抗的干预作用及机制

目的 研究沙棘果油对超抗原诱导的特应性皮炎(AD)小鼠激素抵抗的干预作用,并探讨其作用机制。方法 将50只小鼠按照随机数字表法分为5组,即正常对照组(A组)、模型组(B组)、地塞米松干预组(阳性对照,C组)、沙棘果油干预组(D组)、地塞米松+沙棘果油干预组(E组),每组10只。除A组外,其余各组均采用2,4-二硝基氯苯+葡萄球菌肠毒素B法制备AD小鼠模型。自实验第7天起,分别使用地塞米松(1.5 mg/kg)和/或沙棘果油(10 mL/kg)对C、D、E组小鼠进行灌胃,每天1次,连续28 d。末次给药后,采用苏木素-伊红染色法观察小鼠耳部皮肤组织的病理形态学变化,采用酶联免疫吸附测定法检测小鼠血清中免疫球蛋白E(IgE)、白细胞介素4(IL-4)水平,采用免疫荧光单标法检测小鼠耳部皮肤组织中糖皮质激素受体α(GRα)、GRβ阳性细胞数,采用Western blot法检测小鼠耳部皮肤组织中GRα、GRβ蛋白及蛋白激酶B(AKT)/核糖体蛋白S6激酶1(S6K1)信号通路相关蛋白的表达情况。结果 与B组比较,C、D、E组小鼠左耳部皮肤炎症表现明显减轻;D、E组小鼠血清中IgE、IL-4水平显著降低(P<0.05),GRα阳性细胞数显著增加(P<0.05),核蛋白中GRα蛋白表达水平升高(P<0.05),总蛋白中Gαi1、Gαi3、p-S6K1、pAKT蛋白表达水平均显著降低(P<0.05);E组小鼠GRβ阳性细胞数显著减少(P<0.05),总蛋白中GRβ表达水平显著降低(P<0.05)。与C组比较,E组小鼠左耳部皮肤炎症表现趋于消退,血清中IgE、IL-4水平均显著降低(P<0.05);D、E组小鼠GRα阳性细胞数显著增加(P<0.05),GRβ阳性细胞数显著减少(P<0.05),核蛋白中GRα蛋白表达水平升高(P<0.05),总蛋白中GRβ、Gαi1、p-S6K1、p-AKT的蛋白表达水平及E组小鼠Gαi3的蛋白表达水平均显著降低(P<0.05)。结论 沙棘果油对超抗原诱导的AD小鼠激素抵抗具有干预作用,该作用可能是通过抑制Gαi1/3诱导的AKT/S6K1信号通路而发挥的。

2022年不明原因儿童严重急性肝炎暴发:可能发病机制的分析

截至2022年11月,欧洲地区共22个国家累计报道不明原因儿童严重急性肝炎病例572例。在病例中最常检出的病原体为人腺病毒和新型冠状病毒。研究者们针对这两种病原体提出了可能引起发病的病因假说,但具体病因和致病机制仍尚未明确。本文从病原学及免疫病理的角度对可能引起此次肝炎疫情的致病机制进行了分析,为调查致病机制提供思路。

金黄色葡萄球菌超抗原与特应性皮炎及湿疹关系的初步探讨

目的:探讨皮损部位金黄色葡萄球菌(金葡菌)超抗原(SAg)与特应性皮炎(AD)及湿疹(EC)的关系。方法:反向被动乳胶凝集法测定来自91例AD和174例EC患者皮损共123株金葡菌SAg的产生情况,结合患者的严重度指数(EASI)评分、6种不同皮疹的评分以及血清学指标进行分析。结果:AD组皮损处SAg总阳性率(55.4%)及中毒休克综合征毒素(TSST)-1阳性率(21.4%)均高于EC组(37.3%、4.5%)。AD组内金葡菌肠毒素B(SEB)阳性组EASI评分高于SEB阴性组和金葡菌阴性组。EC组SAg产生与EASI评分无关,但SAg阳性组其皲裂评分较高。AD患者血清白介素(IL)-4、γ干扰素(IFN-γ)及总IgE水平与SAg无关,EC患者SAg阳性组血清总IgE水平高于金葡菌阴性组,IL-4和IFN-γ水平与SAg无关。结论:与EC相比,AD与金葡菌SAg的关系更为密切,某些型别SAg分型与AD临床严重度可能有一定联系。

金黄色葡萄球菌肠毒素B基因的克隆和在大肠杆菌中高效表达

利用PCR方法从金黄色葡萄球菌TSTw基因组DNA中扩增出约 70 0bp的DNA片段 ,将之克隆到pGEM 7Zf(+)载体上并转化大肠杆菌DH5α菌株。重组质粒的测序结果表明克隆到了seb基因 ,它含有 717bp(不包括N端81bp的信号肽编码区 ) ,其核苷酸序列与文献报道完全一致。将其连接于表达载体 7ZTS上 ,转化到大肠杆菌JM10 9(DE3)内。表达的SEB占总蛋白 33.5 %。

超抗原SEA的基因克隆、原核表达与鉴定

目的 构建pRSET SEA重组表达载体 ,转化大肠杆菌BL2 1 (DE3)pLysS ,诱导表达超抗原葡萄球菌肠毒素A(staphylococcalenterotoxinA ,SEA) ,进行分离、纯化及westernblot鉴定。方法 采用PCR技术 ,从产SEA的葡萄球菌标准菌株FRI1 0 0基因组DNA中获得SEA全长序列 ,克隆入pUC1 9中 ,进行测序 ,构建pRSET SEA表达质粒 ,转化大肠杆菌BL2 1 (DE3)pLysS ,通过异丙基硫代 β D 半乳糖苷 (isopropyl beta D thiogalactopyranoside,IPTG)诱导表达 ,分离、纯化及westernblot鉴定。结果 PCR获得超抗原SEA基因片段 ,DNA测序结果与文献报道一致 ;构建了pRSET SEA表达质粒 ,并成功地诱导表达出32 0 0 0u的蛋白 ;Westernblot鉴定所得蛋白能够与SEA单克隆抗体特异性结合。结论 本研究成功地克隆了SEA全长 ,并进行了原核表达和分离、纯化 ,获得了SEA蛋白。

SEA和B7-1基因真核共表达载体的构建及在B16细胞的表达

目的构建葡萄球菌肠毒素A(SEA)和小鼠B71基因真核共表达载体。方法采用PCR和RTPCR方法分别克隆了带B71跨膜区的SEA(SEAB7tm)和小鼠B71基因,中间通过内部核糖体进入位点(Internalribosomeentrysite,IRES)序列的连接克隆至真核表达载体pcDNA3.1+。利用阳离子脂质体将重组质粒转染B16细胞,间接免疫荧光法检测B71和SEA分子在B16细胞膜表面的表达情况。结果测序结果与Genebank中公布的SEA、小鼠B71cDNA序列相符,双标记间接免疫荧光检测结果表明B71、SEA同时在转染的B16细胞膜上表达。结论成功构建了SEA和小鼠B71真核共表达载体,为进一步研究SEA和B71联合应用抗肿瘤免疫治疗及其免疫机理奠定了基础。

内蒙古地区临床型奶牛子宫内膜炎葡萄球菌毒力基因检测及耐药性研究

旨在调查引起内蒙古地区奶牛临床型子宫内膜炎致病葡萄球菌的毒力基因分布情况及其耐药现状。本试验对采集自内蒙古不同地区的260份患有临床型子宫内膜炎奶牛的子宫脓性分泌物进行了葡萄球菌的分离鉴定,调查了超抗原毒素基因(SEs和TSST-1)的分布;采用微量肉汤稀释法测定了19种抗菌药物对分离菌株的MIC,并对红霉素和四环素耐药菌株携带的相关耐药基因进行了检测。结果显示,260份样品中分离到10种127株(48.8%)葡萄球菌,其中金黄色葡萄球菌53株(41.7%),凝固酶阴性葡萄球菌74株(58.3%);80株(63.0%)葡萄球菌至少携带1种超抗原毒素基因,超抗原基因可有17种不同的组合,其中sej(38.6%)检出率最高,sec+sej+sen(33.3%)组合最为流行。分离菌株对青霉素(79.5%)和氨苄西林(71.7%)耐药率最高,对头孢菌素类的耐药率在60%左右,对大环内酯类和四环素抗生素的耐药率均在40%左右,对氟喹诺酮类抗菌药物的耐药率在20%左右,对3种联合用药的抗菌药物组合耐药率均在10%左右,所有菌株均对万古霉素敏感。菌株对红霉素的耐药表型主要由ermC(46.4%)和ermB(37.5%)基因贡献,未检出ermA基因。菌株对四环素的耐药表型主要由tetK(70.0%)基因介导,其次为tetM(10.0%)基因。22株耐甲氧西林葡萄球菌(MRS)均为凝固酶阴性葡萄球菌;MRS菌株对青霉素、氨苄西林、克拉霉素和红霉素的耐药率极显著高于甲氧西林敏感葡萄球菌(MSS)(P<0.01),对头孢噻肟的耐药率高于MSS(P<0.05)。结果提示:内蒙古地区临床型奶牛子宫内膜炎葡萄球菌携带毒力基因复杂,耐药情况较为严重,且发现耐甲氧西林凝固酶阴性葡萄球菌的流行。抗微生物药的耐药性可能是导致内蒙古地区奶牛临床子宫内膜炎治疗失败的主要原因之一。

肝癌靶向性SEA-CD80基因共表达重组腺病毒载体的构建及表达鉴定

目的:构建肝癌靶向性葡萄球菌肠毒素A(SEA)和CD80基因共表达重组腺病毒载体。方法:首先利用现有的腺病毒穿梭质粒pShuttle和pShuttleCMV,构建新的不带CMV增强子/启动子而带有polyA加尾信号穿梭质粒,命名为pShuttle2。将AFP增强子、启动子、SEA及CD80基因分别从已构建的pKSEP载体和pMD18TBIS载体上,分别亚克隆至pShuttle2中,再与腺病毒骨架质粒pAdEasy1共转化E.coliBJ5183。以获得的重组子转染HEK293细胞后制备重组腺病毒,然后感染高表达AFP的肝癌细胞系Hepa16和不表达AFP的黑色素瘤细胞系B16、成纤维细胞系NIH3T3。采用间接免疫荧光法,激光共聚焦显微镜观察和流式细胞术检测SEA和CD80在细胞膜表面的表达。采用3H掺入法检测膜表达的SEA诱导淋巴细胞增殖的活性。结果:以制备的重组腺病毒感染肿瘤细胞后,SEA和CD80能够靶向性地共表达在高表达AFP的Hepa16细胞膜上,而在不表达AFP的B16、NIH3T3细胞膜上不表达。结论:成功地构建肝癌靶向性SEA和CD80基因共表达重组腺病毒载体,为进一步研究SEA和CD80在肝癌靶向基因治疗中的联合应用及其抗肿瘤免疫机制奠定了基础。

重组SEA基因真核表达载体的构建及诱导小鼠抗肝癌免疫的效应

目的 构建葡萄球菌肠毒素A(SEA)真核表达载体 ,并通过体内转染 ,观察其诱导抗小鼠肝癌的免疫效应。方法采用基因工程技术构建SEA基因的真核表达载体 ,使其表达SEA分子。通过阳离子脂质体介导的体内转染 ,观察其对小鼠肝癌的治疗作用。用51 Cr释放法测定治疗组与对照组动物脾淋巴细胞杀伤H2 2 细胞的活性。结果成功地构建了SEA真核表达载体 pLXSN SEA ,体内转染 pLXSN SEA的荷瘤小鼠肿瘤明显缩小 ,生存期延长 ,4 10小鼠肿瘤完全消退 ,且长期无瘤生存。CTL杀伤活性实验表明 ,瘤区内转染pLXSN SEA可诱导强烈的CTL杀伤效应 ,与对照组相比较差异显著 (P <0 .0 1)。结论超抗原SEA体内转染对肿瘤具有明确的治疗作用 。