抗EGFR-抗CD3双功能抗体介导CIK细胞、LAK细胞或PBLS细胞对胃癌荷瘤裸鼠治疗效果的比较

 目的　比较抗EGFR-抗CD3双功能抗体在体内条件下介导CIK细胞、LAK细胞及人类PBLS细胞三类不同的免疫效应细胞对胃癌细胞的杀伤能力,为临床应用该抗体治疗胃癌的细胞选择提供实验指导。方法　采用化学耦联法合成的抗EGFR-抗CD3双功能抗体分别与CIK细胞、LAK细胞及人类PBLS细胞联合经尾静脉注入SGC7901胃癌细胞移植瘤小鼠体内,同时以等量0.9 % NaCl溶液尾静脉注射建立对照,治疗后检测在体情况下4组对胃癌细胞的杀伤能力,进行组间比较。结果　抗EGFR-抗CD3双功能抗体介导CIK细胞治疗组小鼠肿瘤抑制率为（64.9±7.7）%,显著高于抗EGFR-抗CD3双功能抗体介导LAK细胞及人类PBLS细胞组的（43.5±8.2）%和（39.7±6.5）%（均P＜0.05）,治疗结束时平均肿瘤质量为（473.9±37.7）mg,显著低于其他两组的（764.6±88.3）mg和（829.1±104.4）mg（均P＜0.05）。结论　初步的裸鼠模型治疗实验显示由抗EGFR-抗CD3双功能抗体介导的CIK细胞在体内条件下对胃癌治疗作用优于其他常用的免疫效应细胞。     

白桦脂酸对人宫颈癌裸鼠移植瘤的抑制作用及机制

目的 探讨白桦脂酸（BA）对人宫颈癌HeLa细胞株裸鼠皮下移植瘤生长的抑制作用及其机制。方法 将4×10⁶个HeLa细胞接种于裸鼠右肩背部皮下,建立人宫颈癌裸鼠皮下移植瘤模型,24只荷瘤裸鼠随机分为BA高剂量（80mg／kg）、中剂量（40mg／kg）、低剂量（20mg／kg）组及空白对照组（含溶剂）,每组6只,隔日腹腔注射连续给药21d,停药24 h后处死裸鼠,测量裸鼠体重、移植瘤体积、瘤重,计算抑瘤率;光镜下观察移植瘤组织形态学变化;TUNEL法检测肿瘤细胞凋亡指数;免疫组化法检测瘤组织内caspase-3、CytoC蛋白表达。结果 裸鼠处死后,BA处理组的移植瘤体积均明显小于空白对照组（P＜0.01）,其中高、中、低剂量组抑瘤率分别为56.2％、40.4％和24.6％ （P＜0.01）;HE染色法显示BA处理组小鼠的移植瘤组织出现明显凋亡及坏死改变;TUNEL检测对照组和BA低、中、高剂量组的凋亡指数分别为（8.36±2.78）％、（20.98±3.01）％、（28.74±4.77）％和（39.34±6.15）％（P＜0.05）;免疫组化法示BA处理组的肿瘤组织caspase-3、CytoC蛋白表达水平较空白对照组明显升高（P＜0.01）。结论 BA对人宫颈癌HeLa细胞移植瘤的生长具有明显的抑制作用,其机制可能与上调caspase-3、CytoC蛋白的表达及诱导细胞凋亡有关。     

罗格列酮逆转丝裂霉素对人胃癌 SGC7901／VCR祼鼠移植瘤耐药作用的研究

目的：探讨 PPARγ激动剂罗格列酮（ ROS ）逆转人胃癌 SGC7901／VCR 细胞裸鼠移植瘤对丝裂霉素（ MMC）的耐药作用及其可能机制。方法建立人胃癌SGC7901／VCR细胞裸鼠移植瘤模型,将48只裸鼠随机分为6组：空白对照组（生理盐水0．2 ml）、MMC组（ MMC 2．5 mg／kg）、ROS组（ ROS 100 mg／kg）、MMC＋ROS中剂量组（ MMC 2．5 mg／kg＋ROS 50 mg／kg）、MMC＋ROS高剂量组（MMC 2．5 mg／kg＋ROS 100 mg／kg）、MMC＋CSA组（MMC 2．5 mg／kg＋CSA 50 mg／kg）。每组8只裸鼠;用药40天后,观察各组裸鼠体重和移植瘤体积变化,计算抑瘤率,绘制移植瘤的生长曲线;Western-blot法检测P-gp和MGr1-Ag蛋白的表达。结果空白对照组、MMC组移植瘤瘤体积和抑瘤率差异无显著性,ROS组、MMC＋ROS中剂量组、MMC＋ROS高剂量组组、MMC＋CSA组与空白对照组、MMC组比较,移植瘤瘤体积和抑瘤率差异有显著性。空白对照组、MMC组中P-gp、MGr1-Ag蛋白表达最强,ROS组、MMC＋ROS中剂量组、MMC＋ROS大剂量组、MMC＋CSA组与空白对照组和MMC组P-gp、MGr1-Ag蛋白表达比较有统计学意义（ P＜0．05）,MMC＋ROS大剂量组、MMC＋CSA组中其表达最弱,组间差异无统计学意义（P＞0．05）。结论罗格列酮可抑制人胃癌SGC7901／VCR细胞祼鼠移植瘤瘤体生长,罗格列酮可下调人胃癌SGC7901／VCR细胞裸鼠移植瘤组织中P-gp和MGr1-Ag蛋白的表达。罗格列酮可部分逆转人胃癌SGC7901／VCR细胞祼鼠移植瘤对丝裂霉素的耐药性。     

hTERT启动子调控的CD：UPRT／5-FC自杀基因对人胃癌裸鼠移植瘤的抑制作用

目的：研究人端粒酶逆转录酶（hTERT）启动子调控的胞嘧啶脱氨酶：尿嘧啶磷酸核糖转移酶／5-氟胞嘧啶（CD：UPRT／5-FC）融合自杀基因系统在体内对人胃癌SGC7901细胞的杀伤作用。方法：构建胃癌皮下移植瘤模型,随机分成3组处理。观察30天,测量肿瘤体积,计算抑瘤率。肿瘤组织做常规病理检查,免疫组化检测CD蛋白的表达。结果：成功构建胃癌皮下移植瘤模型。治疗30天后,B组（瘤内注射hTERT—CD：UPRT＋腹腔注射PBS）和c组（单纯腹腔注射PBS）的肿瘤生长迅速,肿瘤体积分别为（2．72±0．35）cm’、（2．67-＇i-0．30）tin’,A组（瘤内注射hTERT—CD：UPRT＋腹腔注射5-Fc）的肿瘤生长受到明显抑制,第30天体积为（1．10±0．13）cm’,与前两组相比差异有统计学意义（P〈0．05）,其抑瘤率为59．6％。裸鼠移植瘤病理切片镜检,A组可见大量肿瘤细胞排列稀疏,部分肿瘤细胞核固缩、核碎裂;B组和C组则见大量肿瘤细胞排列紧密,细胞形态和细胞核呈多形性,核大深染,核分裂像多见。免疫组化显示,A组和B组可见CD的表达,C组cD表达呈阴性。结论：hTERT启动子调控的cD：UPRT／5-FC融合自杀基因系统对裸鼠胃癌皮下移植瘤有显著的杀伤作用,为胃癌的基因治疗提供了-种可能的方法。     

蛇葡萄素对人胃癌细胞SGC-7901裸鼠移植瘤生长的抑制作用

目的观察蛇葡萄素(APS)体内抗人胃癌作用。方法采用人胃癌细胞裸鼠移植瘤模型,将裸鼠随机分成5组,APS三个剂量连续灌胃给药10天,观察肿瘤体积、相对肿瘤体积(RTV)、相对肿瘤增殖率（T/C）、瘤重、抑瘤率(IR),以此评价APS的抗肿瘤作用。结果在人胃癌细胞株SGC-7901裸鼠移植瘤的抑瘤实验APS 600mg/kg、300mg/kg、150mg/kg灌胃给药10天,其相对肿瘤增殖率为52.84%、71.12%、62.14%,其抑瘤率分别为38.8%、27.5%、27.3%。结论APS对人胃癌细胞株SGC-7901裸鼠移植瘤有明显的抑制作用。     

hTERT启动子调控的CD:UPRT/5-FC自杀基因对人胃癌裸鼠移植瘤的抑制作用

目的:研究人端粒酶逆转录酶(hTERT)启动子调控的胞嘧啶脱氨酶:尿嘧啶磷酸核糖转移酶/5-氟胞嘧啶(CD:UPRT/5-FC)融合自杀基因系统在体内对人胃癌SGC7901细胞的杀伤作用.方法:构建胃癌皮下移植瘤模型,随机分成3组处理.观察30天,测量肿瘤体积,计算抑瘤率.肿瘤组织做常规病理检查,免疫组化检测CD蛋白的表达.结果:成功构建胃癌皮下移植瘤模型.治疗30天后,B组(瘤内注射hTERT-CD:UPRT+腹腔注射PBS )和C组(单纯腹腔注射PBS)的肿瘤生长迅速,肿瘤体积分别为(2.72±0.35)cm3、(2.67±0.30)cm3,A组(瘤内注射hTERT-CD:UPRT+腹腔注射5-FC)的肿瘤生长受到明显抑制,第30天体积为(1.10±0.13)cm3,与前两组相比差异有统计学意义(P＜0.05),其抑瘤率为59.6%.裸鼠移植瘤病理切片镜检,A组可见大量肿瘤细胞排列稀疏,部分肿瘤细胞核固缩、核碎裂;B组和C组则见大量肿瘤细胞排列紧密,细胞形态和细胞核呈多形性,核大深染,核分裂像多见.免疫组化显示,A组和B组可见CD的表达,C组CD表达呈阴性.结论:hTERT启动子调控的CD:UPRT/5-FC融合自杀基因系统对裸鼠胃癌皮下移植瘤有显著的杀伤作用,为胃癌的基因治疗提供了一种可能的方法.     

MK886在人结肠癌裸鼠模型中的抗血管生成作用

目的通过动物体内实验研究5脂氧合酶活化蛋白（FLAP）抑制剂MK886对人结肠癌的抗血管形成作用,从而进一步探讨其抗肿瘤机制。方法将皮下接种HT-29人结肠癌细胞后建立人结肠癌模型的15只裸鼠随机分为三组,治疗组以MK886溶解在二甲基亚砜中投药;两对照组分别为投以二甲基亚砜和空白对照组。治疗一月后处死裸鼠并取瘤,用免疫组化方法检测各组肿瘤微血管密度,并比较结果。结果15只裸鼠全部成瘤,且实验过程中无一裸鼠死亡;免疫组化检测肿瘤微血管密度结果显示,两对照组肿瘤微血管密度差异无统计学意义（P>0.05）,而治疗组肿瘤微血管密度显著低于两对照组（P<0.05）。结论MK886可通过抑制肿瘤微血管形成抑制人结肠癌的生长。     

蟾毒灵对裸鼠大肠癌原位移植瘤的抗肿瘤作用及其对凋亡相关基因Bcl-xL、Bax表达的影响

目的探讨蟾毒灵对裸鼠大肠癌原位移植瘤的抗肿瘤作用及其可能诱导凋亡的机制。方法将60只人结肠癌细胞株HCT-116建立的裸鼠原位移植瘤模型随机分为生理盐水（NS）组、5-Fu组、蟾毒灵低（BL）、中(BM)、高(BH)5组,每组12只,腹腔注射给药持续7d。用药结束后第24天每组分别处死6只裸鼠,完整取出肿瘤,测量肿瘤大小,计算肿瘤抑制率;剩余裸鼠观察带瘤生存期;TUNEL法检测原位移植瘤细胞的凋亡指数;实时荧光定量PCR法和Western blot法检测凋亡相关基因Bcl-x_L、Bax mRNA和蛋白的表达。结果5-Fu组、BL组、BM组、BH组的肿瘤抑制率分别为69.6%、45.6%、56.2%、58.5%,肿瘤体积与NS组比较明显缩小（P＜0.01);BL组、BM组带瘤生存期与NS组相比较明显延长(P< 0.05)。TUNEL结果显示蟾毒灵用药组的凋亡指数明显高于NS组(P＜0.01）;荧光定量PCR和Western结果显示蟾毒灵可抑制Bcl-x_L基因表达,促进Bax基因表达（P＜0.05）。结论蟾毒灵对裸鼠大肠癌原位移植瘤有显著的抗肿瘤作用,能够抑制Bcl-xL基因和促进Bax基因表达,诱导肿瘤细胞凋亡可能是蟾毒灵抗肿瘤的重要机制之一。     

声敏剂Sonoflora介导的声动力治疗小鼠S180肉瘤的实验研究

目的探讨声敏剂Sonoflora在S180肉瘤荷瘤小鼠肿瘤组织中的聚集情况及联合超声介导的声动力疗法（SDT）对S180肉瘤的杀伤作用。方法（1） S180肉瘤荷瘤小鼠腹腔注射10mg／kg的Sonoflora,分别于3、6、12、18、24、48、72h处死小鼠,利用共聚焦显微镜（LSCM）观察Sonoflora在肿瘤及正常肌肉组织中的聚集情况。（2） 荷瘤小鼠分别给予超声、Sonoflora及超声联合Sonoflora处理,以腹腔注射生理盐水作为空白对照组。每2天测量肿瘤体积大小,15天后剥离肿瘤组织,比较瘤体重量。 结果 腹腔给药18h后,Sonoflora在肿瘤和正常肌肉组织中的含量均达最高峰,且差异最明显,肿瘤组织中的荧光强度是正常肌肉组织的5.33倍,给药18h为最佳的超声辐射时间。单独使用超声照射（0.4、0.8、1.6W／cm²）或单独注射Sonoflora（10、20、40mg／kg）对小鼠 S180肉瘤无明显杀伤作用。Sonoflora（10mg／ml）联合超声0.4W／cm²（S1U1）、0.8W／cm²（S1U2）、1.6W／cm²（S1U3）组的瘤重（g）分别为2.30±0.40、0.94±0.44、0.88±0.28,分别较空白对照、单纯超声及单纯Sonoflora组显著减少,差异均有统计学意义（P＜0.05）。S1U1组的瘤重均低于S1U2、S1U3组,差异有统计学意义（P＜0.05）,而S1U2组与S1U3组比较,差异无统计学意义（P＞0.05）。结论 Sonoflora具有肿瘤靶向聚集性,其联合超声介导的SDT对小鼠 S180肉瘤有明显杀伤作用。     

健择联合电子线照射对人胰腺癌裸鼠移植瘤凋亡的影响

目的探讨健择联合电子线外照射对人胰腺癌细胞株(panc-1)裸鼠移植瘤细胞凋亡的作用。方法建立人胰腺癌panc-1裸鼠移植瘤模型,36只裸鼠随机分为6组：对照组（A组）、单纯放疗组(B组)、健择25mg/kg组(C组)、健择50 mg/kg组(D组)、联合治疗1组（E组）、联合治疗2组（F组）。A组裸鼠尾静脉注射0.9%氯化钠溶液,B组荷瘤鼠背部肿瘤局部以6MeV电子线照射。C、D组分别以25 mg/kg、50 mg/kg健择裸鼠尾静脉注射,E、F组分别以25、50 mg/kg健择裸鼠尾静脉注射加背部肿瘤6MeV电子线照射。采用TUNEL法检测凋亡指数（AI）,免疫组织化学检测凋亡抑制蛋白Bcl-2、凋亡相关蛋白Bax的表达情况。结果干预组较对照组肿瘤细胞凋亡明显增加,干预组各组之间凋亡指数比较差异有统计学意义（P＜0.05）。免疫组织化学结果示：与对照组比较,干预各组均可不同程度下调Bcl-2蛋白表达,Bax蛋白表达上调（P＜0.05）,联合治疗组与其他各组比较,Bcl-2蛋白表达降低,Bax蛋白表达升高,差异均有统计学意义（P ＜0.05）。结论健择联合电子线对人胰腺癌移植瘤的凋亡有促进作用。     

Anti-CD3 x anti-epidermal growth factor receptor (EGFR) bispecific antibody redirects T-cell cytolytic activity to EGFR-positive cancers in vitro and in an animal model.

PURPOSE: Targeting epidermal growth factor receptor (EGFR) overexpressed by many epithelial-derived cancer cells with anti-EGFR monoclonal antibodies (mAb) inhibits their growth. A limited number of clinical responses in patients treated with the anti-EGFR mAb, (cetuximab), may reflect variability in EGFR type or signaling in neoplastic cells. This study combines EGFR-targeting with the non-MHC-restricted cytotoxicity of anti-CD3 activated T cells (ATC) to enhance receptor-directed cytotoxicity. EXPERIMENTAL DESIGN: ATC from normal and patient donors were expanded ex vivo. Specific cytolytic activity of ATC armed with anti-CD3 x anti-EGFR (EGFRBi) against EGFR-expressing cancer cells derived from lung, pancreas, colon, prostate, brain, skin, or EGFR-negative breast cancer cells was evaluated in (51)Cr release assays. In vivo studies comparing tumor growth delay induced by EGFRBi-armed ATCs or cetuximab were done in severe combined immunodeficient/Beige mice (SCID-Beige) bearing COLO 356/FG pancreatic and LS174T colorectal tumors. RESULTS: At effector/target ratios from 3.125 to 50, both EGFRBi-armed normal and patient ATC were significantly more cytotoxic, by 23% to 79%, against EGFR-positive cells over ATC, cetuximab, anti-CD3 alone, or ATC armed with irrelevant BiAb directed at CD20. EGFRBi-armed ATC also secreted significantly higher levels of some T(H1)/T(H2) cytokines compared with ATC alone. In mice, i.v. infusions of EGFRBi-armed ATC (0.001 mg equivalent/infusion) were equally effective as cetuximab (1 mg/infusion) alone for significantly delaying growth of established COLO 356/FG but not LS174T tumors compared with mice that received ATC alone or vehicle (P < 0.001). CONCLUSIONS: Combining EGFR antibody targeting with T cell-mediated cytotoxicity may overcome some limitations associated with EGFR-targeting when using cetuximab alone.     

EGFR单克隆抗体治疗转移性结直肠癌的耐药分子机制

靶向表皮生长因子受体（EGFR）的单克隆抗体是转移性结直肠癌（mCRC）的重要治疗药物,但有效率并不理想,主要原因是存在严重的原发性和继发性耐药。本文从分子改变的方面就靶向EGFR单克隆抗体（anti EGFR mAb）治疗mCRC的耐药分子机制作一综述,旨在为进一步研究anti EGFR mAb耐药机制提供参考,为mCRC患者实现临床个体化治疗提供理论依据。     

Induction of intercellular adhesion molecule 1 on small cell lung carcinoma cell lines by gamma-interferon enhances spontaneous and bispecific anti-CD3 x antitumor antibody-directed lymphokine activated killer cell cytotoxicity.

The interaction between LFA-1 and its natural ligand, ICAM-1, plays an important role in leukocyte adhesion and signal transduction. LFA-1-mediated T-cell adhesion is generally activated by CD3-mediated signal in association with T-cell receptor-mediated recognition of the antigen/major histocompatibility complex on antigen-presenting cells. In the present study, we compared spontaneous or bispecific antibody (BsAb)-directed LAK cell cytotoxicity against ICAM-1+ or ICAM-1- small cell lung cancer (SCLC) cell lines. gamma-Interferon (IFN-gamma)-induced ICAM-1 expression on ICAM-1- SCLC cell lines, and susceptibility to LAK cells was increased simultaneously. Increased cytolysis of the IFN-gamma-treated SCLC was inhibited by an anti-ICAM-1 monoclonal antibody (mAb). Furthermore, LAK cell cytotoxicity directed by BsAb, which was composed of OKT3 and anti-SCLC mAb, was also increased by the IFN-gamma treatment of SCLC, and this increase was inhibited by an anti-ICAM-1 mAb but not by anti-Class I or anti-CD2 mAb. These results suggest that a prior administration of IFN-gamma would enhance the efficacy of the following specific targeting therapy utilizing BsAb and LAK cells by up-regulating the ICAM-1 expression on tumor target cells. The combinational use of IFN-gamma and anti-CD3 x anti-tumor BsAb might be a promising way of enhancing LAK cell-mediated adoptive immunotherapy in small cell lung cancer patients.     

NRP -1 b1/b2单克隆抗体对裸鼠胃癌移植瘤生长的影响

目的：探讨神经纤毛蛋白1（neuropilin -1,NRP -1）在胃癌细胞 BGC823中的表达情况,并观察自主研发的抗 NRP -1 b1/ b2单克隆抗体（NRP -1 mAb）对裸鼠胃癌移植瘤生长的影响。方法：基于实验室前期已成功制备出纯度和浓度均较高的 NRP -1 mAb。利用流式细胞术检测该抗体亲和性、细胞免疫荧光定位检测 NRP -1的分布及 NRP -1 mAb 特异性。建立胃癌移植瘤裸鼠模型,向移植瘤中注射不同浓度的 NRP -1 mAb,研究抗体对胃癌裸鼠皮下移植瘤生长的影响。2周后根据瘤体大小得出抑瘤率。最后免疫组化分析癌组织内血管内皮生长因子（VEGF）的表达情况。结果：胃癌细胞 BGC -823上存在 NRP -1,且主要分布在细胞膜上,能与自制的 NRP -1 mAb 有效结合。通过动物实验,NRP -1 mAb 能有效抑制移植瘤的生长,高浓度抗体较低浓度对移植瘤抑制作用更明显,NRP -1 mAb 治疗组中 VEGF 表达较空白组低（P <0.01）。结论：胃癌细胞 BGC -823细胞膜上表达 NRP -1,NRP -1 mAb 能特异性结合胃癌细胞上 NRP -1蛋白,NRP -1 mAb 能抑制胃癌裸鼠移植瘤的生长,且与浓度呈正相关,可能与下调 VEGF 表达有关。     

Inhibition of acute myeloid leukemia cell growth by mono-specific and bi-specific anti-CD33 x anti-CD64 antibodies

Bi-specific anti-CD33 x anti-CD64 antibodies (BsAb) mediated more potent and longer-lasting inhibition of proliferation of human leukemia cell lines and primary acute myeloid leukemia (AML) samples compared to mono-specific anti-CD33 mAb. There were no differences between these two antibodies in cellular internalization over time. The inhibitory effect of BsAb was mimicked by a mouse IgG2a subclass mono-specific anti-CD33 mAb. These findings indicate that enhanced inhibition of proliferation was caused by simultaneous ligation of both CD33 and CD64 molecules. We conclude that inhibition of leukemia cell growth initiated by BsAb during prolonged exposure may have therapeutic value for the treatment of AML.     

Human c-erbB-2 proto-oncogene product as a target for bispecific-antibody-directed adoptive tumor immunotherapy.

To develop an efficient strategy for the targeting of anti-tumor effector cells, we prepared bispecific antibody (BsAb) containing anti-CD3 and an anti-c-erbB-2 proto-oncogene product. The prepared BsAb specifically reacts with both c-erbB-2-positive tumor cells and CD3+ CTL. Human CD4+ helper/killer T cells, induced from peripheral-blood mononuclear cells by activation with immobilized anti-CD3 monoclonal antibody (MAb) plus IL-2, showed no significant cytotoxicity against tumor cells. However, treatment of human CD4+ helper/killer cells with the BsAb caused the induction of specific cytotoxicity against c-erbB-2-positive tumor cells. CD4+ helper/killer cells also produced significant amounts of IL-2 during co-culture with c-erbB-2-positive tumor cells in the presence of the BsAb. Moreover, by combination with the BsAb, CD4+ helper/killer cells showed a strong in vivo anti-tumor effect against c-erbB-2 transfectant or human colon-cancer cells implanted in nude mice. Our results strongly suggest that the c-erbB-2 proto-oncogene product on human tumor cells may be a good target for BsAb-directed adoptive tumor immunotherapy.     

抗CD3／抗TNP双功能抗体的制备及对胃癌细胞系的杀伤作用

 目的　以化学方法将抗CD3及抗三硝基苯(TNP)单克隆抗体交联为双功能抗体,研究此双功能抗体与任何TNP化的抗肿瘤单抗结合,介导对肿瘤细胞的杀伤作用。方法　分别纯化抗CD3及抗TNP单克隆抗体,经二硫苏糖醇(DTT)还原、偶联得到抗CD3/抗TNP双抗。TNP化抗胃癌单抗PD4、3H11与抗CD3/抗TNP双抗介导人淋巴细胞对胃癌细胞系MGC803的细胞毒作用。结果　双抗与TNP化的单抗结合,介导效应细胞对靶细胞的杀伤率高于未TNP化单抗,并随着效靶比的提高而升高。结论　抗CD3/抗TNP双抗能够与不同种类的TNP化单抗结合介导效应细胞杀伤靶细胞,有潜在的临床应用价值。     

Anti-HER-2 anti-CD3 bi-specific antibodies inhibit growth of HCT-116 colorectal carcinoma cells in vitro and in vivo

Objective: This study is conducted to evaluate the effects of anti-HER-2×anti-CD3 bi-specific antibodies(BsAb)on HER-2/neuover-expressing human colorectal carcinoma cells. Methods: Growth was assessed by MTT assaysafter exposure of HCT-116 cells to Herceptin, anti-CD3 and BsAb antibodies. Immunocytochemistry was appliedto test the HER-2 level of HCT-116. In a nude mouse model, HER-2×CD3 BsAb was combined with effectorcells (peripheral blood lymph cells from normal human being) for observations on in Vivo growth of tumors.Results: Compared with the control group, using effector cells combined with anti-CD3 McAb, Herceptin orHER2×CD3 BsAb, tumor cell growth in vitro and in vivo was significantly inhibited (P<0.05), most remarkablyin the HER2×CD3 BsAb case. The growth of xenografts with HER2×CD3 BsAb combined with effector cells wasalso significantly inhibited when compared with the anti-CD3 McAb or Herceptin groups (P<0.05). Conclusion:HER-2/neu might be a useful target for immunotherapy in colorectal carcinoma, anti-HER2×anti-CD3 BsAbexerting clear anti-tumor effects.     

分子靶向药物给药模式对转移性结直肠癌患者生存的影响

目的 探讨两种不同类型靶向药物在不同给药模式下对转移性结直肠癌（mCRC）患者生存的影响。方法 回顾性分析135例接受过分子靶向治疗mCRC患者的临床病理特征、靶向治疗情况及随访资料,比较不同种类靶向药物及不同线数化疗联合靶向治疗对生存期（OS）的影响。结果 全组中接受抗EGFR单抗者、接受贝伐珠单抗者及接受抗EGFR单抗+贝伐珠单抗者的中位OS依次为20.7、24.4和41.6个月,接受两种靶向药物者比仅接受一种靶向药物者的中位OS有明显延长（P＜0.05）;一线化疗未联合靶向治疗者的中位OS为30.8个月,与一线化疗联合靶向治疗者的21.5个月相比,差异无统计学意义（P＞0.05）;三线及以上联合靶向治疗者的中位OS为37.0个月,高于三线前均联合靶向治疗者的137个月,差异有统计学意义（P＜0.05）;接受过三种化疗药物（伊立替康、奥沙利铂、氟尿嘧啶）及贝伐珠单抗和抗EGFR单抗两种靶向药物的患者中,三线及以上使用靶向者的中位OS为50.6个月,与三线前使用靶向者的41.6个月比较,差异无统计学意义（P＞0.05）。结论 接受过两类靶向药物治疗的mCRC患者比仅接受一类靶向药物者可能获得更好生存获益。患者使用靶向药物的时机并非越早越好,肿瘤生物学行为较好的患者更适合先化疗后靶向的治疗模式。