双特异抗体COC183B_2×anti-CD28对卵巢上皮癌细胞杀伤效力的研究

目的 :检测双特异抗体 (bispecificantibody ,BsAb)COC183B2 ×anti CD2 8在体外介导预激活的外周血单个核细胞 (PBMC)对卵巢上皮癌细胞系SKOV3的杀伤效力。方法 :在大肠杆菌中对用基因工程方法构建的COC183B2 ×anti CD2 8进行诱导表达 ,用ELISA方法测定表达产物与卵巢癌抗原和CD2 8抗原结合的活性后 ,与SKOV3和预激活的PBMC共孵育。 6h后用非放射性细胞毒分析试剂测定预激活的PBMC对SKOV3细胞毒性作用 ,并在镜下观察SKOV3的形态学改变。结果 :ELISA结果显示 ,COC183B2 ×anti CD2 8可与卵巢癌抗原和CD2 8抗原双向结合 ;细胞毒性试验显示 ,在体外COC183B2 ×anti CD2 8能介导预激活的PBMC特异杀伤SKOV3细胞 ;4h时镜下可见玫瑰花环形成 ,12h可见肿瘤细胞溶解。结论 :COC183B2 ×anti CD2

Phase I study of chimeric anti-CD20 monoclonal antibody in Chinese patients with CD20-positive non-Hodgkin＇s lymphoma

Objective： This study was designed to determine the safety, pharmacokinetics and biologic effects of a humanmouse chimeric anti-CD20 monoclonal antibody （SCT400） in Chinese padents with CD20-positive B-cell non- Hodgkin＇s lymphoma （CD20 B-cell NHL）. SCT400 has an identical amino acid sequence as rituximab, with the exception of one amino acid in the CH1 domain of the heavy chain, which is common in Asians. Methods： Fifteen patients with CD20＋ B-cell NHL received dose-escalating SCT400 infusions （250 mg/m2： n=3; 375 mg/m2： n=9; 500 mg/m2： n=3） once weekly for 4 consecutive weeks with a 24-week follow-up period. The data of all patients were collected for pharmacoklnetics and pharmacodynamics analyses. Results： No dose-limiting toxicities were observed. Most drug-related adverse events were grade 1 or 2. Two patients had grade 3 or 4 ncutropenia. Under premedication, the drug-related infusion reaction was mild. A rapid, profound and durable depletion of circulating B cells was observed in all dose groups without significant effects on T cell count, natural killer （NK） cell count or immunoglobulin levels. No patient developed anti- SCT400 antibodies during the course of the study. SCT400 serum half-life （Tin）, maximum concentration （Cmax and area under the curve （AUC） generally increased between the first and fourth infusions （P〈0.05）. At the 375 mg/m2 dose, the T1/2 was 122.5±46.7 h vs. 197.0,75.0 11, respectively, and the Cmax was 200.6±20.2 pg/mL vs. 339.1±71.0 ng/mL, respectively. From 250 mg/m2 to 500 mg/m2, the Cmax and AUC increased significantly in a dose-dependent manner （P〈0.05）. Patients with a high tumor burden had markedly lower serum SCT400 concenmations compared with those without or with a low tumor burden. Of the 9 assessable patients, 1 achieved complete response and 2 achieved partial responses. Conclusions; SCT400 is well-tolerated and has encouraging preliminary efficacy in Chinese patients with CD20＋ B-cell NHL.

Time-Programmed Delivery of Sorafenib and Anti-CD47 Antibody via a Double-Layer-Gel Matrix for Postsurgical Treatment of Breast Cancer

The highly immunosuppressive microenvironment after surgery has a crucial impact on the recurrence and metastasis in breast cancer patients.Programmable delivery of immunotherapy-involving combinations through a single drug delivery system is highly promising,yet greatly challenging,to reverse postoperative immunosuppression.Here,an injectable hierarchical gel matrix,composed of dual lipid gel(DLG)layers with different soybean phosphatidylcholine/glycerol dioleate mass ratios,was developed to achieve the time-programmed sequential delivery of combined cancer immunotherapy.The outer layer of the DLG matrix was thermally responsive and loaded with sorafenib-adsorbed graphene oxide(GO)nanoparticles.GO under manually controlled near-infrared irradiation generated mild heat and provoked the release of sorafenib first to reeducate tumor-associated macrophages(TAMs)and promote an immunogenic tumor microenvironment.The inner layer,loaded with anti-CD47 antibody(aCD47),could maintain the gel state for a much longer time,enabling the sustained release of aCD47 afterward to block the CD47-signal regulatory proteinα(SIRPα)pathway for a long-term antitumor effect.In vivo studies on 4T1 tumor-bearing mouse model demonstrated that the DLG-based strategy efficiently prevented tumor recurrence and metastasis by locally reversing the immunosuppression and synergistically blocking the CD47-dependent immune escape,thereby boosting the systemic immune responses.

Expression of Anti-CD4 Human/Murine Chimeric Antibody and Their Killer Tumor Activity

From the mouse hybridoma cell line secreting an anti-CD4 monoclonal antibody (McAb), total RNA was prepared. The VH and VL genes were amplified by RT-PCR with family specific primer pairs. The PCR products were cloned into pGEM-T vectors, then tranfected into JM109. The VH and VL genes were snalyzed by automatic DNA sequencer. According to Kabat classification, the VH and VL genes belong to the mouse ig heavy subgroup Ⅱ(A) and x chain subgroupⅢ, respectively. The VH and VL genes were subcloned into pr1-Expr and Pk Expr respectively, then transfected into XL2-Blue. The VH- Pr1 and VL- pk were trans feeted by electroporation into mouse myeloma cell X63Ag8. 653. The transfectoma cells were selected by G418 screening, and then supernatant of cultured transfectoma were analyzed by ELISA and immunofluorescence techniques.We have acquired transfectoma cells secreting anti-CD4 chimeric antibodies.These chimeric antibodies are able to kill tumor cells specifically in vitro.

Tumor neoangiogenesis detection by confocal laser endomicroscopy and anti-CD105 antibody:Pilot study

AIM: To evaluate neoangiogenesis in patients with colon cancer by two fluorescently labeled antibodies on fresh biopsy samples imaged with confocal laser endomicroscopy(CLE).METHODS: CLE is an imaging technique for gastrointestinal endoscopy providing in vivo microscopy at subcellular resolution.An important question in validating tumor angiogenesis is what proportion of the tumor vascular network is represented by preexisting parent tissue vessels and newly formed vessels.CD105(endoglin) represents a proliferation-associated endothelial cell adhesion molecule.In contrast to panendothelial markers,such as CD31,CD105 is preferentially expressed in activated endothelial cells that participate in neovascularization.Thus,we evaluated CD105 and CD31 expression from samples of ten patients with primary rectal adenocarcinoma,using a dedicated endomicroscopy system.A imaging software was used to obtain the Z projection of the confocal serial images from each biopsy sample previously combined into stacks.Vascular density and vessel diameters were measured within two 50 μm x 475 μm rectangular regions of interest centered in the middle of each image in the horizontal and vertical direction.The results were averaged over all the patients and were expressed as the mean ± SE.RESULTS: The use of an anti-CD105 antibody was found to be suitable for the detection of blood vessels in colon cancer.Whereas anti-CD31 antibodies stained blood vessels in both normal and pathologic colon equally,CD105 expression was observed primarily in malignant lesions,with little or no expression in the vessels of the normal mucosa(244.21 ± 130.7 vessels/mm3 in only four patients).The average diameter of antiCD105 stained vessels was 10.97 ± 0.6 μm in tumor tissue,and the vessel density was 2787.40 ± 134.8 vessels/mm3.When using the anti-CD31 antibody,the average diameter of vessels in the normal colon tissue was 7.67 ± 0.5 μm and the vessel density was 3191.60 ± 387.8 vessels/mm3,while in the tumors we obtained an average diameter of 10.88 ± 0.8 μm and a vessel density of 4707.30 ± 448.85 vessels/mm3.Thus,there were more vessels stained with CD31 than CD105(P < 0.05).The average vessel diameter was similar for both CD31 and CD105 staining.A qualitative comparison between CLE vs immunohistochemistry lead to similar results.CONCLUSION: Specific imaging and quantification of tumor microvessels are feasible in human rectal cancer using CLE examination and CD105 immunostaining of fresh tissue samples.

Inhibitory Effect of Anti-HER-2 Anti-CD3 Bi-specific Antibody on the Growth of Gastric Carcinoma

To evaluate the effect of anti-HER-2 × anti-CD3 bi-specific antibody（BsAb） on the growth of HER-2/neu-expressing human gastric carcinoma in vitro and in vivo, an MTT assay was carried out to test the inhibitive rates of herceptin, anti-CD3 and BsAb antibodies on SGC-7901 gastric carcinoma cells. Immunocytochemistry methods were used to test the HER-2 level of SGC-7901. Nude mice models were employed to test the effect of HER-2 CD3 BsAh combined with effector ceils（ peripheral blood lymphatic cells of healthy human beings） on the growth of tumors in animals. Compared with that of the untreated control group, the tumor cell growth rates in vitro and in vivo will both be significantly inhibited when treated with effector cells combined with anti-CD3 McAb, herceptin or HER2 CD3 BsAb （p 〈0. 05）, and the growth inhibition is the most remarkable in the group treated with HER2 CD3 BsAb combined with effector cells. The growth of tumor xenografts will also be significantly inhibited in the group treated with HER2 CD3 BsAb combined with effector cells when compared with that in the group treated with anti-CD3 McAb or the group treated with herceptin combined with effector cells（p 〈0. 05）. We can conclude that HER-2/neu is possibly a useful target for immunotherapy of gastric carcinoma, and anti-HER2 × anti-CD3 BsAb has evident anti-tumor efficacy both, in vitro and in vivo.

重组鼠IL-28的原核表达、纯化及多克隆抗体的制备

目的：获取重组鼠IL-28（m IL-28）纯化蛋白,制备多克隆抗体。方法：用PCR技术扩增鼠IL-28成熟蛋白的编码序列,克隆入原核表达载体pET-30,构建融合表达载体pET-30 a-m IL-28,转化大肠埃希菌BL21（DE3）,以IPTG诱导表达IL-28融合蛋白,经镍柱亲和层析纯化,然后免疫6-8周龄鸡,制备多克隆抗体,采用ELISA检测抗体效价。结果：成功构建了表达载体pET-30 a-m IL-28,DNA序列测定结果与预期结果一致。在37℃培养条件下,IPTG诱导表达的IL-28融合蛋白进行SDS-PAGE电泳分析,发现其与融合蛋白的理论计算值一致,免疫鸡后收获抗血清,ELISA显示抗体效价具有高度特异性。结论：获得了重组鼠IL-28纯化蛋白,制备了鼠IL-28多克隆抗体,为进一步深入研究IL-28的生物活性及其应用打下基础。

联合应用CD3/CD28单克隆抗体对小鼠T淋巴瘤细胞EL4活化的影响

目的:研究联合应用CD3/CD28单克隆抗体对小鼠T淋巴瘤细胞EL4活化的影响。方法:ELISA方法检测不同浓度CD3/CD28抗体在不同时间点体外刺激EL4细胞后培养上清中IL-2的分泌;CCK-8方法检测EL4细胞增殖能力;流式细胞术检测EL4细胞周期;RT-PCR检测IL-2、NF-κB和NF-AT转录因子的转录情况。结果:在48小时抗CD3抗体(25μg/ml)与抗CD28抗体(2μg/ml)共刺激EL4细胞明显增加IL-2的分泌和细胞增殖能力,不影响细胞周期。结论:EL4细胞可以作为研究小鼠T淋巴瘤细胞活化的细胞模型。

UROC28基因的原核表达及抗UROC28多抗制备和初步应用

目的 :在原核细胞大肠杆菌中融合表达UROC2 8基因产物 ,分离、纯化后制备其特异性多克隆抗体 ,并初步应用于肿瘤标本的检测 ,为进一步研究该分子的功能和组织分布等提供条件 .方法 :利用DNA重组技术将UROC2 8基因克隆入融合表达载体pRSET c质粒 ,并在大肠杆菌BL 2 1中融合表达目的蛋白 ,回收后制备兔抗血清 ,Westernblot鉴定抗体后 ,应用该抗体对前列腺癌石蜡切片进行免疫组化染色 .结果 :His UROC2 8融合蛋白的Mr 约为 2 2 0 0 0 ,与预期相符 ;融合蛋白占菌体总蛋白的 2 0 % .目的蛋白免疫新西兰兔获得多克隆抗体 ,Westernblot结果显示制备的抗UROC2 8多克隆抗体具有较高的特异性 ,无明显交叉反应 ,并成功在前列腺癌组织标本中检测UROC2 8的表达 .结论 :本研究成功构建了UROC2 8融合表达载体 ,并在大肠杆菌中获得高效表达 .制备了该分子的多克隆抗体 ,经初步验证其效价高、特异性好 ,为深入研究UROC2

Induction of specific immunosuppression of cardiac allograft rejection withmonoclonal antibodies to CD44, LFA-1 and ICAM-1

Objective:To evaluate the immunosuppressive effect of monoclonal antibodies (McAb) against cell surface adhesion molecules on transplant rejection. Methods: C57BL/6 (H-2b) mouse cardiac grafts were transplanted into BALB/c(H- 2d) mice. This model was used to investigate the possibility of immunosuppressive induction with CD44 McAb, leukocyte function associated antigen (LFA-1) and intercellular adhesion molecule (ICAM-1). Results: Treatment of the allograft recipients with CD44 McAb alone, or both LFA-1 and ICAM-1 or combination of these 3 McAb significantly prolonged the cardiac allografts survival as compared with PBS controls (P<0.01). The combination of anti-CD44 and ICAM-1 and LFA-1 McAb was shown to produce more significant prolongation of grafts survival than anti-CD44 McAb alone or both anti-ICAM- 1 and LFA-1 McAb (P < 0.01). Histological examination of the grafts treated with the McAb displayed greatly reduced mononuclear cell infiltration. The proliferation of spleen cells from recipient BALB/c with McAb treatment was significantly inhibited in response to the stimulators of C57BL/6 spleen cells, but increased upon the stimulation of C3H/He (H-2k) spleen cells, as demonstrated by mixed lymphocyte reaction. Similarly, the cytotoxic activity against donor H-2-compatible (H-2b) target cells, EL-4 cells, was significantly suppressed. The spleen cells from allografted recipient BALB/c mice with McAb treatment induced specific tolerance for C57BL/6 cardiac grafts in allografted recipients, whereas those from allografted BALB/c mice without McAb treatment induced acute rejection. Conclusion: These results indicate that antiadhesion therapy using a combination of McAb to adhesion molecules can induce specific immunosuppression of transplant rejection.

Effect of panel reactive antibodies on T cell immunity reinstatement following renal transplantation

BACKGROUND Chronic kidney disease is associated with immunological disorders,presented as phenotypic alterations of T lymphocytes.These changes are expected to be restored after a successful renal transplantation;however,additional parameters may contribute to this process.AIM To evaluate the impact of positive panel reactive antibodies(PRAs)on the restoration of T cell phenotype,after renal transplantation.METHODS CD4CD28null,CD8CD28null,natural killer cells(NKs),and regulatory T cells(Tregs)were estimated by flow cytometry at T0,T3,and T6 which were the time of transplantation,and 3-and 6-mo follow-up,respectively.Changes were estimated regarding the presence or absence of PRAs.RESULTS Patients were classified in two groups:PRA(-)(n=43)and PRA(+)(n=28)groups.Lymphocyte and their subtypes were similar between the two groups at T0,whereas their percentage was increased at T3 in PRA(-)compared to PRA(+)[23(10.9-47.9)vs 16.4(7.5-36.8)μ/L,respectively;P=0.03].Lymphocyte changes in PRA(-)patients included a significant increase in CD4 cells(P<0.0001),CD8 cells(P<0.0001),and Tregs(P<0.0001),and a reduction of NKs(P<0.0001).PRA(+)patients showed an increase in CD4(P=0.008)and CD8(P=0.0001),and a reduction in NKs(P=0.07).CD4CD28null and CD8CD28null cells,although initially reduced in both groups,were stabilized thereafter.CONCLUSION Our study described important differences in the immune response between PRA(+)and PRA(-)patients with changes in lymphocytes and lymphocyte subpopulations.PRA(+)patients seemed to have a worse immune profile after 6 mo follow-up,regardless of renal function.

血清抗突变型瓜氨酸波形蛋白抗体在类风湿关节炎诊断中的价值

目的探讨抗突变型瓜氨酸波形蛋白(MCV)抗体在类风湿关节炎(RA)诊断中的价值。方法采用ELISA法测定68例RA患者(RA组)、62例关节疼痛及自身免疫性疾病患者(疾病对照组)、129例健康体检者(正常对照组)的抗MCV抗体、抗环瓜氨酸肽(CCP)抗体水平,计算抗MCV抗体与抗CCP抗体诊断RA的敏感性与特异性;速率散射比浊法检测CRP水平,记录压痛关节数(TJC)、肿胀关节数(SJC),并计算DAS28积分值。对抗MCV抗体与抗CCP抗体及DAS28积分(包括CRP、TJC、SJC三个变量)进行Spearman秩相关性分析。结果 RA组抗MCV抗体、抗CCP抗体、DAS28积分值显著高于疾病对照组及正常对照组;抗MCV抗体与抗CCP抗体诊断RA的敏感性分别为88.2%(60/68)、75.0%(51/68),P=0.026;特异性分别为97.3%(186/191)、95.8%(183/191),P=0.548。抗MCV与抗CCP抗体呈显著正相关(r=0.826,P<0.05);抗MCV与RA活动度指标DAS28积分及CRP、肿胀关节数间均有明显相关性。结论抗MCV抗体在RA诊断中较抗CCP抗体具有更高的敏感性和特异性,能为RA诊断提供良好的依据,且抗MCV抗体与RA病情活动度指标相关,高滴度的抗MCV可能在一定程度上提示RA的病情活动。

抗CCP抗体与类风湿关节炎临床表现的相关性

目的:探讨抗环瓜氨酸肽抗体(抗CCP抗体)与类风湿关节炎(RA)的临床表现的相关性。方法:收录139例RA患者的临床表现及X线分期。以酶联免疫吸附(ELISA)法测定其抗CCP抗体水平,抗类风湿因子(RF)采用乳胶凝集法测定,魏氏法测定血沉(ESR)。结果:抗CCP抗体阳性患者在血沉的分布(阴性vs阳性)、X线分期的分布(Ⅰ+Ⅱ期vsⅢ+Ⅳ期)、关节外表现的分布(<3个vs≥3个)、DAS 28评分的分布(>5.1分vs≤5.1分)方面与抗CCP抗体阴性患者比较,差异均有高度统计学意义(χ2=14.89、6.87、14.63、7.27,均P<0.01)。结论:抗CCP抗体与病情活动的指标(血沉、DAS 28评分)有关,与RA患者关节破坏程度(X线分期)和关节外表现有关。

人胰腺癌组织胚胰腺泡蛋白表达的免疫组织化学研究

用ＡＢＣ免疫组织化学法，以单克隆抗体Ｊ（２８）检测胰腺癌等组织中的胚胰腺泡蛋白（ＦＡＰ）。结果：正常胰腺（５例）基本无ＦＡＰ表达；慢性胰腺炎阳性率为６０．００％（６／１０），强度为；胚胎胰腺６例中全部为阳性强度；胰腺癌阳性率为７３．６８％（１４／１９），强度为；而肝胰壶腹癌（１例）、胰岛细胞瘤（１例）及胰腺转移性腺癌（５例）无ＦＡＰ表达。胰腺癌ＦＡＰ表达强度较慢性胰腺炎强（Ｐ＜０．０５）。本研究表明ＦＡＰ在胚胎胰腺中存在，正常胰腺消失，胰腺癌及慢性胰腺炎时可以再表达，其表达可能与胰腺细胞的增殖分化有关。

RF及抗CCP抗体与类风湿关节炎骨侵蚀及肺间质纤维化的关系分析

目的:探讨类风湿因子(RF)、抗环瓜氨酸(CCP)抗体与类风湿关节炎(RA)疾病活动性评分及关节损害、肺间质纤维化的关系。方法分析抗 CCP抗体、RF与类风湿关节炎活动性评分(DAS28)、关节骨侵蚀、肺间质纤维化的关系。结果合并肺间质纤维化的 RA患者中,RF高滴定度阳性(19.2%)所占百分比高于阴性者(11.5%),抗CCP抗体高滴定度阳性(66.7%)所占百分比高于阴性者(14.8%),差异有统计学意义(P<0.05)。结论高滴定度RF和抗CCP抗体可能与RA患者合并肺间质纤维化相关。

Anti-cd TCR antibody-expanded cd T cells:a better choice for the adoptive immunotherapy of lymphoid malignancies

Cell-based immunotherapy for lymphoid malignancies has gained increasing attention as patients develop resistance to conventional treatments.cd T cells,which have major histocompatibility complex(MHC)-unrestricted lytic activity,have become a promising candidate population for adoptive cell transfer therapy.We previously established a stable condition for expanding cd T cells by using anti-cd T-cell receptor(TCR)antibody.In this study,we found that adoptive transfer of the expanded cd T cells to Daudi lymphoma-bearing nude mice significantly prolonged the survival time of the mice and improved their living status.We further investigated the characteristics of these antibody-expanded cd T cells compared to the more commonly used phosphoantigen-expanded cd T cells and evaluated the feasibility of employing them in the treatment of lymphoid malignancies.Slow but sustained proliferation of human peripheral blood cd T cells was observed upon stimulation with anti-cd TCR antibody.Compared to phosphoantigen-stimulated cd T cells,the antibody-expanded cells manifested similar functional phenotypes and cytotoxic activity towards lymphoma cell lines.It is noteworthy that the anti-cd TCR antibody could expand both the Vd1 and Vd2 subsets of cd T cells.The in vitro-expanded Vd1 T cells displayed comparable tumour cell-killing activity to Vd2 T cells.Importantly,owing to higher C–C chemokine receptor 4(CCR4)and CCR8 expression,the Vd1 T cells were more prone to infiltrate CCL17-or CCL22-expressing lymphomas than the Vd2 T cells.Characterizing the peripheral blood cd T cells from lymphoma patients further confirmed that the anti-cd TCR antibody-expanded cd T cells could be a more efficacious choice for the treatment of lymphoid malignancies than phosphoantigen-expanded cd T cells.

Treatment strategies for nodal and gastrointestinal follicular lymphoma:Current status and future development

In recent years,therapies for follicular lymphoma (FL) have steadily improved.A series of phase Ⅲ trials comparing the effect of rituximab with chemotherapy vs chemotherapy alone in treating FL have indicated significant improvements in progression-free survival (PFS) and overall survival.Recent studies have found that prolonged response durations and PFS were obtained with maintenance therapy using rituximab or interferon after completion of first line therapy.For patients with relapsed or refractory FL,phase Ⅱ studies have assessed the effectiveness of combination therapies using a Toll-like receptor-9 agonist (1018ISS),oblimersen sodium (a Bcl-2 antisense oligonucleotide),bendamustine,and rituximab,as well as veltuzumab,a new humanized anti-CD20 antibody,and epratuzumab.In addition,the effectiveness of yttrium-90 ibritumomab tiuxetan and iodine-131 tositumomab as radioimmunotherapies has been reported.Furthermore,three phase Ⅲ studies on an idiotype vaccine are near completion.Unfortunately,these vaccines,which appeared highly effective in phase Ⅰ and Ⅱ trials,do not appear to result in prolonged PFS.This report will summarize the current knowledge on therapies for treatment of FL,and will conclude with a brief discussion of feasiblefuture options for effective treatments.Lastly,we added descriptions of the management of gastrointestinal FL,which is considered to be controversial because it is rare.

A multi-center,open-label,randomized,parallel-controlled phase II study comparing pharmacokinetic,pharmacodynamics and safety of ripertamab(SCT400)to rituximab(Mab Thera?)in patients with CD20-positive B-cell non-Hodgkin lymphoma

Objective:This multi-center,open-label,randomized,parallel-controlled phaseⅡstudy aimed to compare the pharmacokinetics(PK),pharmacodynamics(PD)and safety profile of ripertamab(SCT400),a recombinant antiCD20 monoclonal antibody,to rituximab(MabThera^(■))in patients with CD20-positive B-cell non-Hodgkin lymphoma(NHL).Methods:Patients with CD20-positive B-cell NHL who achieved complete remission or unconfirmed complete remission after standard treatment were randomly assigned at a 1:1 ratio to receive a single dose of ripertamab(375mg/m^(2))or rituximab(MabThera^(■),375 mg/m^(2)).PK was evaluated using area under the concentration-time curve(AUC)from time 0 to d 85(AUC_(0-85d)),AUC from time 0 to week 1(AUC0-1 w),AUC from time 0 to week 2(AUC_(0-2 w)),AUC from time 0 to week 3(AUC_(0-3 w)),AUC from time 0 to week 8(AUC_(0-8 w)),maximum serum concentration(C_(max)),terminal half-life(T_(1/2)),time to maximum serum concentration(T_(max))and clearance(CL).Bioequivalence was confirmed if the 90%confidence interval(90%CI)of the geometric mean ratio of ripertamab/rituximab was within the pre-defined bioequivalence range of 80.0%-125.0%.PD,immunogenicity,and safety were also evaluated.Results:From December 30,2014 to November 24,2015,a total of 84 patients were randomized(ripertamab,n=42;rituximab,n=42)and the PK analysis was performed on 76 patients(ripertamab,n=38;rituximab,n=38).The geometric mean ratios of ripertamab/rituximab for AUC_(0-85d),ATC_(0-inf),and Cmaxwere 96.1%(90%CI:87.6%-105.5%),95.9%(90%CI:86.5%-106.4%)and 97.4%(90%CI:91.6%-103.6%),respectively.All PK parameters met the pre-defined bioequivalence range of 80.0%-125.0%.For PD and safety evaluation,there was no statistical difference in peripheral CD 19-positive B-cell counts and CD20-positive B-cell counts at each visit,and no difference in the incidence of anti-drug antibodies was observed between the two groups.The incidences of treatment-emergent adverse events and treatment-related adverse events were also comparable between the two groups.Conclusions:In this study,the PK,PD,immunogenicity,and safety profile of ripertamab(SCT400)were similar to rituximab(MabThera^(■))in Chinese patients with CD20-positive B-cell NHL.

Targeting and Internalization of Sterically Stabilized Liposome Modified with ZCH-4-2E8

Sterically stabilized liposome （SL） modified with 2E8 monoclonal antibody （2E8-SL） was prepared in order to evaluate its targeting ability and internalization efficiency against tumor cells with high expression of CD19.2E8 was coupled to the surface of SL using post-insertion technique. The shape of liposomes was observed under a transmission electronic microscope. The average size of liposomes was determined by using the Zetasizer instrument. The binding and internalization of 2E8-SL against tumor cells with higher expression of CD 19 were tested by flow cytometry and confocal microscopy. The mean diameter of 2E8-SL was 121.25 nm. 2E8-SL was stable after up to 24 days in various buffers. 2ES-SL showed specific binding to tumor cells with high expression of CD19, including B cells in peripheral blood mononuclear cells （PBMCs）. 2E8-SL could efficiently internalize into Nalm6 cells with CD19 high expression. It is suggested that 2E8-SL may serve as useful delivery carrier of anti-cancer drugs targeting to hematological malignant tumors with CD 19 high expression.

抗CCP抗体对类风湿关节炎的诊断意义及其与病情关系

目的检测对比类风湿关节炎(RA)病例组和对照组患者血液中抗环瓜氨酸肽(CCP)抗体和类风湿因子(RF)的水平,系统评价能用于RA准确诊断、病情监测和预后判断的相关血清学指标。方法将患者按标准分为病例组和对照组。检测两组患者血液中抗CCP抗体和RF的水平,对两者在两组患者中阳性检出率差异性进行比较,并分析两者联合检测的特点。比较分析抗CCP抗体浓度与RA患者DAS 28评估得分的关系,分析抗CCP抗体浓度与疾病进展的相关性。结果 RA患者中抗CCP抗体阳性率高于非RA患者,差异有统计学意义(χ~2=102.820,P=0.000<0.050)。RA患者中RF阳性率高于非RA患者,差异有统计学意义(χ~2=18.687,P=0.000<0.050)。单独检测抗CCP抗体的灵敏度为69.47%,特异度为88.61%;RF的灵敏度为77.10%,特异度为47.46%;两者串联检测的灵敏度为58.02%,特异度为90.51%;并联检测时灵敏度为84.73%,特异度为46.20%。准确诊断RA时并联实验应用价值较高。抗CCP抗体的浓度与RA患者的DAS 28评估分值两者呈正相关(R=0.907)。结论对于RA的诊断抗CCP抗体和RF并联实验是一种很好的检测方法。抗CCP抗体浓度与患者DAS 28评估得分高度相关,可用于临床疾病进展判断和用药指导。