^131I—抗AFP—MMC“双弹头”导向治疗原发性肝癌毒副反应观察

目的：研究“双弹头”导向治疗原发性肝癌毒副反应。方法：用１３１Ｉ－抗ＡＦＰ－ＭＭＣ“双弹头”导向治疗原发性肝癌２９例（５４例次），用自身对照设计（单组比较设计），全组１３１Ｉ－平均治疗剂量为６２．０９×１０７Ｂｑ，（２１．５３～１４９．１１）×１０７Ｂｑ。结果：治疗后外周血象无明显变化，心和肾功能正常，肝功能ＡＬＴ有７例轻度升高；甲状腺功能Ｔ３、Ｔ４值下降分别有３例和１例，过敏反应出现３例。结论：本组治疗耐受性良好，毒副反应轻微。     

131碘标记肝癌单抗片段介入治疗原发性肝癌的临床毒副作用观察

目的 观察^131碘标记肝癌单抗片段介入治疗原发性肝癌的临床毒副作用。方法采用股动脉插管介入治疗方法对25例原发性肝癌患者进行42人次的^131碘标记肝癌单抗片段的导向治疗，分别于治疗前以及治疗后7天、28天、36天、57天观察血常规、尿常规、肝功、肾功、甲功，并进行统计分析。结果治疗前后各项指标变化较小。结论通过介入方法临床应用^131碘标记肝癌单抗片段治疗原发性肝癌，方法安全无明显毒副作用。     

“双弹头”抗AFP抗体对肝癌导向综合治疗的实验和临床研究

为增强导向治疗的“弹头”杀伤力，提高肝癌导向综合治疗的疗效，对马抗人ＡＦＰ抗体进行了１３１Ⅰ和丝裂霉素（ＭＭＣ）双标记，制备同时携带１３１Ⅰ和ＭＭＣ的“双弹头”马抗人ＡＦＰ抗体（１３１Ⅰ－ＡＦＰＡｂ－ＭＭＣ）。荷人肝癌裸鼠的定位显像和抑癌率实验显示１３１Ⅰ－ＡＦＰＡｂ－ＭＭＣ具有良好的定位显像作用，抑癌率达７３．５％，明显高于对照组（Ｐ＜０．０５）。２２例配对的中晚期原发性肝癌患者的“双弹头”导向综合治疗结果：治疗组的有效率（ＣＲ＋ＰＲ＋ＭＲ）为６３．２％明显高于对照组（３１．８％），Ｐ＜０．０５；治疗组的１年生存率（５２．６％）亦明显高于对照组（２２．７％）Ｐ＜０．０５，且无严重毒副作用。表明：１３１Ⅰ－ＡＦＰＡｂ－ＭＭＣ的“双弹头”导向综合治疗可提高中晚期原发性肝癌的疗效     

~（131）Ⅰ－抗AFP抗体导向治疗肝癌的临床观察

１９８０～１９９３年，用（１３１）Ⅰ－抗ＡＦＰ抗体治疗不能切除肝癌７２例（１５３例次），治疗≥２次占４７例，平均（１３１）Ⅰ量为３１．８７（６．４～９７．４）Ｍｃｉ，中位数２７．４ｍｃｉ（１０１３．８ＭＢｑ）。结果：总有效率２０．８％（１５／７２），治后一年生存率３３．３％（２２／６６）；治疗≥２，≥３，≥４次者有效率分别为２９．８％（１４／４７）、６０．０％（９／１５）和７０．０％（７／１０）；一年生存率依次为４５．７％、７３．３％和８０．０％；瘤大小：≤７ｃｍ，７．１～１０ｃｍ和＞１０ｃｍ患者，治后瘤缩小率分别为１００．０％、７６．９％和５３．９％；一年生存率８７．５％、４８．０％和１５．４％；经肝动脉灌注治疗有效率高于ｉｖ给药者（６４．３％：１５．２％），一年生存率亦高于ｉｖ（６４．３％：３７．５％）。本研究表明，（１３１）Ⅰ－抗ＡＦＰ抗体导向治疗肝癌具有明显疗效。     

^131I—chTNT单克隆抗体瘤体内注射治疗肺癌疗效观察

目的：观察^131I-chTNT(^131I标记的肿瘤标记细胞核单克隆抗体）瘤体内注射治疗肺癌的疗效和毒性。方法：25例肺癌患者采用^131I-chTNT注射液,每人2次,每次0.8mCi/kg瘤体内直接注射。结果：有效率48％,CR：8％,PR：40％。仅2例发生气胸,骨髓抑制0－Ⅱ度。结论：^131I-chTNT瘤体内注射疗效高,毒副反应轻,值得进一步应用观察。     

^131I抗AFP抗体导向治疗肝癌的临床观察

１９８０－１９９３年，用＾１３１Ｉ－抗ＡＦＰ抗体治疗不能切除肝癌７２例（１５３例次），治疗≥２次占４７例，平均＾１３１Ｉ量为３１．８７（６．４－９７．４）Ｍｃｉ，中粒数２７．４ｍｃｉ（１０１３．８ＭＢｑ）。结果：总果：总有效率２０．８％（１５／７２），治后一年生存率３３．３％（２２／６６）；治疗≥２，≥３，≥４次者有效率分别为２９．８％（１４／４７），６０．０％（９／１５）和７０．０％（７／１０）     

131I-chTNT导向治疗晚期肺癌的临床研究

目的分析并评价131I肿瘤细胞核人鼠嵌合单克隆抗体(131I-chTNT)对晚期肺癌的治疗作用,选择最佳的给药途径.方法 43例肺癌患者均经细胞学或病理学证实,其中ⅢB期30例,Ⅳ期13例;初治32例,复治11例.采用三种途径给药(1)静脉组22例;(2)瘤体组16例;(3)瘤体+静脉组5例.131I-chTNT剂量均按2.96×107Bq/kg计算,每人2次,间隔2周.结果完全缓解(CR)2例(4.7%),部分缓解(PR)11例(25.6%),总有效率为30.2%(13/43).其中静脉组有效率为9.1%,瘤体组有效率为56.3%,有显著性差异(P＜0.01).主要毒性为骨髓抑制,其中Ⅲ度白细胞下降仅占4.7%(2/43),Ⅲ度血小板下降占7.0%(3/43),均为静脉组.结论 131I-chTNT对晚期肺癌有一定的疗效,瘤体内注药为最佳给药方式.     

~（131）I美妥昔单抗治疗79例原发性肝癌的近期疗效及毒副作用观察

目的：总结131I美妥昔单抗（商品名：利卡汀）治疗中晚期原发性肝癌（HCC）的近期疗效及毒副作用。方法：已确诊的HCC患者79例,采用经肝动脉途径灌注利卡汀治疗。治疗后每月随访患者一般情况、影像学改变、甲胎蛋白（AFP）、肝功能、外周血白细胞、血小板变化等。对治疗前不同肝功能分级患者复发情况进行比较,评价近期疗效及毒副作用。结果：利卡汀治疗后71例随访的患者中1个月无复发率为100%,3个月无复发率为76.1%,6个月无复发率为28.2%。所有患者中死亡14例,占19.2%,中位生存时间8个月。均未发生与治疗药物相关的严重并发症。结论：131I美妥昔单抗用于不可手术切除肝癌患者,尤其是肝功能情况较好患者的疗效明显;是原发性肝癌治疗中的一种新型、有效的治疗方法。     

转铁蛋白受体单克隆抗体与导向碘油混悬剂治疗中晚期肝癌的疗效观察

转铁蛋白受体单克隆抗体与表阿霉素、顺铂等药物制成偶联物后再与碘油制成导向碘油混悬剂，称之为＂双重载体＂，利用介入技术治疗失去手术机会的中晚期肝癌患者２３例，总缓解率应为６９．５６％。＂双重载体＂的假说能否成立，有待探讨。     

肝癌干细胞抗体靶向治疗的实验

目的研究抗人肝癌干细胞鼠单抗15B7的生物学特征、体内外功能,探讨靶向肝癌干细胞是否能够有效抑制肝癌移植瘤复发、自发性肺转移以及延长荷瘤小鼠的生存期。方法采用双色免疫荧光、双色流式细胞技术、皮下成瘤实验,检测、鉴定15B7单克隆抗体能够识别肝癌干细胞(hepatocellular carcinomacancer stem cells, HCC-CSC)。从人肝癌细胞系BEL7402中以流式细胞仪分选具有CD133+或ESA+表型的细胞。在此基础上采用CCK-8细胞增殖实验、侵袭实验、迁移实验等检测分析15B7单抗对CD133+表型的细胞增殖、侵袭、迁移的作用以及对细胞周期的影响。裸鼠体内治疗实验研究15B7单抗对BEL7402移植瘤生长的抑制作用。以Western blot方法鉴定该功能性单抗的抗原。结果双色免疫荧光和双色流式检测显示15B7单抗能与HCC-CSC的标志物ESA、CD133共染;流式分选15B7+或ESA+或CD133+的细胞在体外无血清培养条件下有良好的成球生长能力;流式分选的15B7+细胞裸鼠皮下接种1×104个/只,2月可形成肿瘤,以上实验证明15B7单抗是抗肝癌干细胞的单抗。体外功能实验结果显示15B7单抗能够抑制CD133+细胞的增殖、迁移、侵袭,抑制率分别达13.8%、157%和30.9%,同时还能诱导CD133+细胞发生G1期阻滞。体内治疗实验研究结果表明15B7单抗能明显抑制裸鼠肝癌移植瘤生长,抑制率可达60.5%。Western blot显示15B7单抗识别HCC-CSC表达的抗原蛋白相对分子质量约50 kD。结论15B7单抗能明显抑制裸鼠体内人肝移植瘤的生长,为肝癌干细胞的靶向治疗提供有重要应用价值的候选抗体药物。     

单克隆抗体12H6的靶抗原在肺癌细胞中的表达及功能研究

[目的]分析抗肺癌单抗12H6的靶抗原在肺癌细胞系和肺癌组织中的表达,研究单抗12H6体内外生物学功能.[方法]细胞免疫荧光、流式细胞荧光法检测单抗12H6靶抗原在3种肺癌细胞系中的表达及其定位,免疫组化法检测其在人肺癌组织中表达及特异性;Transwell法和CCK-8法分别检测12H6体外对肺癌细胞系侵袭和增殖功能的影响.共接种模型裸鼠体内治疗实验研究12H6对移植瘤生长的抑制作用.[结果]单抗12H6的靶抗原在人肺腺癌细胞(A549、GLC-82)、人肺鳞癌细胞(GLC-P)的胞内及胞膜均有表达,在3种细胞系胞膜的表达比例分别为31.2％、15.4％和16.7％.单抗12H6在人肺癌组织中的表达比例为80.6％,较配对癌旁组织显著上调.单抗12H6在体外能明显抑制肺癌细胞侵袭和增殖;体内能明显抑制移植瘤生长,抑制率为40％.[结论]单抗12H6具有优良的体内外抑瘤功能,可能为肺癌靶向治疗提供潜在的靶向治疗药物.     

Anti-murine Antibody Response to Mouse Monoclonal Antibodies in Cancer Patients

Although development of human anti-murine inununoglobulin antibody (HAMA) is often seen in patients receiving murine antibodies, the variety of methods used for detecting HAMA makes it difficult to compare directly the HAMA responses measured by different assays. In the present study, several parameters of the HAMA response to two murine monoclonal antibodies were evaluated. The anti-sialosyl Tn antibody MLS102 and anti-CA125 antibody 145-9, which were labeled with ¹¹¹ln, were injected intravenously into 17 colorectal cancer patients and 11 ovarian cancer patients for immnnoscintigraphy, respectively. HAMA was measured by enzyme-linked immunosorbent assay. There was no difference in baseline HAMA levels before antibody injection between the two groups. HAMA developed more frequently in ovarian cancer patients receiving the 145-9 antibody than in colorectal cancer patients receiving the MLS102 antibody (9/11 vs. 6/17, P <0.05). No significant difference was observed in maximal HAMA levels between the two groups of patients. However, time to reach the maximal levels was delayed and the duration of the response seemed longer in ovarian cancer patients. Among 11 patients receiving the 145-9 antibody three patients became positive for HAMA more than 2 months after antibody injection and the other two had HAMA activity in their sera for more than 17 months. HAMA response was different between the two antibodies, and late onset or long duration of HAMA response against the 145-9 antibody suggests the importance of HAMA measurement in patients who receive a second injection of murine antibodies even after a long interval.     

中晚期原发性肝癌患者血浆可溶性P-选择素的测定及临床意义

目的 :探讨sP -selectin与原发性肝癌发展及转移的关系以及化疗对原发性肝癌患者血浆中sP -se lectin水平的影响。方法 :用ELISA法检测54例中晚期原发性肝癌患者化疗前后血浆sP -selectin的含量。结果 :中晚期原发性肝癌患者化疗前后血浆中可溶性P -selectin均明显高于正常对照组(P<0 01) ;而且与原发性肝癌的临床分期及治疗效果有关 ,Ⅲ期患者较Ⅱ期患者高(P<0 05) ,治疗前较治疗后高(P<0 05)。结论 :中晚期原发性肝癌患者血浆可溶性P -selectin含量比正常人高 ,而且随着病情的发展及疗效而改变 ,故检测sP -selectin有可能成为原发性肝癌辅助诊断、病情发展及疗效观察的一项有价值的指标     

A Monoclonal Antibody, KM10 Reactive with Human Gastrointestinal Cancer and Its Application for Immunotherapy

A monoclonal antibody, KM10 (IgG₁) was produced by fusing spleen cells from a human gastric cancer cell (MKN45)-primed BALB/c mouse with the murine myeloma cell line X63-Ag8-653. The antibody reacted strongly with the plasma membrane of human gastrointestinal carcinoma. Sections of the malignant and benign tissues were tested with immunoperoxidase. All of 10 (100%) large intestinal cancers, 26 of 31 (84%) gastric cancers, 5 of 7 (71%) pancreatic cancers and all of 3 (100%) ampullary cancers reacted positively. Moderate or weak reactivity was observed with normal human tissues, hepatoma and carcinomas of mammary, thyroid and adrenal glands. According to a study of the distribution of ¹²⁵I-labeled KM10 in nude mice bearing human gastric cancer, KM10 selectively localized in tumor tissue rather than normal tissue. Whole body autoradiography also supported such a selective distribution. Destruction of antigenic properties by pronase digestion demonstrated its protein nature and by Western blot analysis, it was identified as a protein with an Mr of 180–200 kd. KM10-adriamycin (ADM) conjugate was prepared via an oxidized dextran bridge and this immunoconjugate retained the binding activity against human gastric cancer. MKN45 cells were inoculated subcutaneously into athymic mice and intravenous treatment was begun when the tumor became measurable. A dose-dependent antitnmor activity was observed in vivo with KM10-ADM conjugate, while this conjugate was less toxic than free ADM.     

胃癌单克隆抗体3H11的应用

胃癌单克隆抗体(McAb)3H11具有高阳性反应率、高选择性及高亲和力的特点.以~(131)I标记后注入荷胃癌裸鼠模型中,其瘤/肝比可达8.26±1.26,定位指数达6.08 ±1.51,ID%/g达11.00±2.62.该McAb与~(131)I偶联后可明显增强后者对肿瘤的杀伤效应及减低毒副反应.~(131)I标记的McAb 3H11静脉注入19例拟行手术的胃癌患者中,16例获阳性显像(84.2%).经胃镜引导注入癌旁粘膜下行胃癌放射免疫导向手术,判别胃壁肿瘤浸润的灵敏度、特异性及准确率分别为946%,967%及959%.判别淋巴结转移的上述指标分别为99.2%、97.7%及98.8%.     

Bispecific Monoclonal Antibody Therapy of B-Cell Malignancy

Bispecific monoclonal antibodies (bsAbs) that recognize CD3 with one arm and a tumor associated antigen with the other arm can retarget T-cells toward tumor cells in an MHC independent manner, thereby combining the specificity of monoclonal antibodies with the power of the cellular immune system. B-cell malignancies are particularly attractive as targets for anti-CD3-based bsAb therapy because of their sensitivity to other forms of antibody therapy, and the extent to which B-cells and T-cells communicate at the molecular level. BsAbs that recognize CD3 and a number of antigens on malignant B-cells have been shown in vitro to be capable of retargeting T-cells. In animal models of B-cell malignancy, bsAb can eliminate tumor loads that are resistant to unmodified monoclonal antibody therapy. Ongoing early clinical trials in advanced B-cell lymphoma indicate CD3-based bsAbs have significant biologic effects, and suggest they have anti-tumor activity as well. A number of significant questions relating to bsAb therapy of B-cell malignancies remain. It is unclear what role both endogenously produced and exogenously administered cytokines are likely to play. Further exploration of whether bsAb can induce T-cells to target to tumor will also be required before the true promise of this novel form of immunotherapy can be determined.     

晚期甲状腺癌治疗的曙光——靶向和免疫治疗

近年来,甲状腺癌的发病率显著增加,大多数病例以分化型甲状腺癌为主,其特点是预后良好。然而,在初始治疗后仍有15%的患者出现疾病持续或复发,并且局部晚期或转移性癌症患者对既定治疗无效,最终有死亡的风险。国内外对于晚期甲状腺癌的治疗仍有争议,但都倾向于靶向和免疫治疗为主的综合治疗。随着对甲状腺癌分子发病机制的深入理解,临床上已批准了多种新的靶向治疗方法用于晚期甲状腺癌。中国临床肿瘤学会(CSCO)2021年指南和欧洲肿瘤内科学会(ESMO)2022年指南(更新)均将靶向治疗作为晚期甲状腺癌治疗的Ⅰ级推荐。本文将对晚期甲状腺癌临床治疗新进展作一综述。