Enhanced clearance of radiolabeled murine monoclonal antibody by a syngeneic anti-idiotype antibody in tumor-bearing nude mice.

A syngeneic anti-idiotype monoclonal antibody (MAb) (CM-11) directed against an anti-carcinoembryonic antigen (CEA) murine MAb (NP-4) was evaluated as a second antibody (SA) to promote the rapid clearance of radiolabeled NP-4 from the blood. Initial studies confirmed that CM-11 IgG removed 131I-NP-4 IgG from the blood as effectively as a polyclonal donkey anti-goat IgG removed 131I-goat IgG. However, use of an F(ab')2 in place of either the NP-4 or CM-11 IgG was not as effective in removing primary radiolabeled antibody, despite the formation of high-molecular-weight complexes. In accordance with previous results, the timing and dose of the SA injection was critical for optimizing tumor uptake and improving tumor/non-tumor ratios. In nude mice bearing GW-39 human colonic tumor xenografts, a delay in the injection of CM-11 by 48 hr after injection of radiolabeled NP-4 was optimal, since this allowed maximum tumor accretion. At a 200:1 CM-11:NP-4 ratio, tumor uptake was reduced, suggesting inhibition of NP-4 binding to CEA within the tumor. Despite optimizing tumor uptake by delaying SA injection and adjusting its dose, the percentage of 131I-NP-4 in the tumor decreased 2- to 3-fold within 2 days after CM-11 injection. A similar effect was seen for 111In-labeled NP-4 IgG with CM-11. Injection of excess unlabeled NP-4 given to block CM-11 shortly after its injection failed to curtail the loss of NP-4 from the tumor. Our results suggest that high blood levels of MAb are important for sustaining NP-4 in the tumor. Radiation-dose predictions derived from biodistribution studies indicate that a higher tumor dose may be delivered using the SA method than with either 131I-NP-4 IgG or F(ab')2 alone. Use of the SA method with 90Y-labeled NP-4 IgG, as modeled from biodistribution studies with 111In-NP-4 IgG, would likely be limited by liver toxicity.     

抗人肺腺癌单克隆抗体在荷瘤裸鼠体内的分布及肿瘤放射免疫显象

Biodistribution and radioimmunoimaging of monoclonal antibody, 5F11, against human lung adenocarcinoma (LTEP-a2) in tumor-bearing nude mice were studied. The binding rate of radioiodinated 5F11 with LTEP-a2, as determined by in vitro binding assay, was 27.64 +/- 5.01%, while the control was less than 5.0%, suggesting that 5F11 reacted specifically with LTEP-a2. Seventy-two, 96 and 120 hr after injection of 125I-5F11, the percentage of dose taken per gram tumor tissue was 4.84%, 6.29% and 6.60%, higher than those of all normal organs. From 48 to 120 hr on, the ratio of tumor to normal tissue (T/NT) in the liver, spleen, kidney, stomach and intestine was more than 2; T/NT in the lung was 3.1-4.7; T/NT in the blood increased gradually and was 1.87 at 96 after injection. Tumor location index was 4.16, while that of the normal tissue was only 1.21. These results showed that human lung adenocarcinoma xenografts in nude mice were specifically located by radioiodinated 5F11. Radioimmunoimaging was performed in tumor-bearing nude mice. The tumors were clearly visualized 72 hr after injection of 131I-5F11. Radioactivity was higher in tumor region than in other regions. The optimal imaging time was 72-96 hr after injection of radioiodinated 5F11.     

^I31I标记抗胃癌单克隆抗体3G9在荷瘤裸鼠体内定位的研究

3G9 is one of murine monoclonal antibodies against human gastric cancer produced by immunization of multiple human gastric cancer cell lines in sequence in our institute. In vitro 3G9 had a high specific binding capacity with human gastric cancer tissues and cell lines. 131I-labeled 3G9 and 125I-labeled normal murine IgG were injected into nude mice bearing xenograft or cells M85 and MGC803 of human gastric cancer in order to compare the differences between 3G9 and IgG distributions in tumor and various normal tissues. The distribution of radioactivity in vivo suggested that 131I-3G9 had a good ability of localization in tissues of gastric cancer. The tumor/blood, tumor/liver, tumor/stomach and tumor/muscle ratios were 1.23, 4.72, 7.25 and 10.28, respectively. The localization index of tumor was 2.62 at 48 hr and 4.13 at 96 hr. The radioactivity of 125I-IgG in tumor was much lower than that of 131I-3G9 and tended to decrease with time. The results of scintigraphy showed that there was distinct radioactivity in the tumor. In this group of nude mice, the minimum weight and diameter of tumor was 83 mg and 4 mm, respectively. The method of scintigraphy to analyse variation of radioactivity in tumor-bearing nude mice was established. The results showed that monoclonal antibody 3G9 could be useful in localization and treatment of human gastric cancer.     

Localization and imaging of radiolabelled monoclonal antibody against squamous-cell carcinoma of the head and neck in tumor-bearing nude mice

Nude mice carrying human squamous-cell carcinoma xenografts were given i.v. injections of radiolabelled monoclonal antibodies (MAbs). MAb E 48, which reacts with squamous-cell carcinomas, was labelled with 131I, while a second control MAb of similar immunoglobulin subclass was labelled with 125I. Both antibodies were injected simultaneously, then the mice were scanned with a gamma camera or their tissues were removed and antibody uptake was calculated as a percentage of the injected dose. Uptake of E 48 reached a peak value of 16%/g on day 3, while uptake of the control antibody was less than 1.8%/g. By 24 hr after injection tumor could be visualized without subtraction techniques. At days 3 and 7, only xenografts were visible on imaging. These findings suggest that E 48 is capable of high specificity in targeting isotopes to squamous-cell carcinomas in an experimental setting.     

Tumour-growth suppression in nude mice by a murine monoclonal antibody: factors hampering successful therapy.

The murine MAb C215 has been shown to mediate ADMMC in vitro and to have a tumour-growth-suppressive effect on xenografted COLO 205 human colocarcinoma cells in nude mice. To overcome the limitations of MAb therapy, it is necessary to understand the underlying mechanisms of tumour-growth suppression. In the present work, we have used C215 to define the importance of different parameters involved in tumour therapy with murine IgG2a antibodies. The results show that there exists a period of roughly 2 days after inoculation into animals during which the tumour cells are sensitive to an inhibitory antibody-mediated effect. After this initial period, the in-vivo sensitivity of tumour cells to antibody-mediated inhibition is much reduced. Tumour cells can remain "dormant" and, despite ongoing antibody treatment, develop into tumours with a reduced growth rate, which is not caused by outgrowth of antigen-deficient tumour cells. Finally, a pronounced dependence of antibody-mediated tumour suppression on antibody dose was observed.     

Inhibition of the growth of human melanoma metastases in nude mice by melanoma-specific murine monoclonal antibody.

The administration of anti-melanoma murine monoclonal antibody (MAB) 16.C8 (IgG2a) to nude mice bearing established human melanoma lung or liver metastases resulted in a significant inhibition of tumour growth. A total dose of 2 mg of affinity purified 16.C8 caused complete inhibition of tumour growth in 89 and 100% of animals in the liver and lung model, respectively. In contrast, a significant tumour growth was found in most control animals which received an irrelevant IgG2a MAB or 2% human serum albumin in Hanks Balanced Salt Solution (HBSS). The MAB was most effective when treatment was started on day 1 or 4 following tumour inoculation. When the 16.C8 MAB treatment was delayed 7 or 14 days, 33 and 67% of 16.C8 treated animals, respectively, developed tumours. The MAB-mediated anti-tumour activity appeared to be dose dependent, and the effect of a suboptimal dose was potentiated by the concomitant administration of recombinant interleukin 2 (rIL-2). Recombinant IL-2 alone in a similar dose did not elicit comparable anti-tumour activity. Moreover, the MAB 16.C8 inhibited tumour growth in irradiated animals which may suggest the involvement of host-radioresistant cellular elements in the 16.C8 antibody-mediated anti-tumour activities in nude mice. These results suggest that MAB 16.C8 alone or combined with rIL-2 may prove useful in the immunotherapy of metastatic melanoma.     

Localization and imaging of radiolabeled monoclonal antibodies against colorectal carcinoma in tumor-bearing nude mice

Four monoclonal antibodies (MoAbs) (35, 115, 17-1A, and B72.3) directed towards human carcinoma surface antigens have been studied in athymic nude mice with LS174T, CO112, or SW948 colon carcinoma xenografts or negative control melanoma (MEL-1), lymphoma (Namalwa), and breast (MCF-7) carcinoma xenografts to evaluate the effects of antigenic heterogeneity and time after administration on localization and imaging. 125I-labeled 115 showed the highest uptake of any antibody in LS174T tumors. MoAbs 35 and B72.3 showed similar but lower levels of uptake in LS174T and CO112 tumors, but B72.3 concentrated less in SW948 tumors. 17-1A showed the highest degree of accumulation in SW948 tumor xenografts. No specific uptake of the four anti-carcinoma MoAbs was observed in MEL-1, Namalwa, or MCF-7 xenografts. The specificity of the in vivo tumor localization of the four anti-carcinoma MoAbs was confirmed by the low degree of accumulation of a control MoAb against influenza virus in LS174T tumors. Imaging studies with 131I-labeled colorectal cancer MoAbs showed specific uptake and retention in LS174T tumors, with progressive clearance from the whole body. The colorectal cancer MoAbs were compared for immunohistochemical binding against biopsies from patients with colorectal cancer and adjacent normal colonic tissue. Most colorectal cancer specimens showed moderate to strong staining with the four MoAbs. The percentage of positive cells varied within and between tumors demonstrating antigenic heterogeneity. Absent to slight focal staining was seen with normal colon tissue. B72.3 showed the highest degree of staining specificity. This study indicates a difference in the immunohistochemical binding of a panel of MoAbs against biopsies of colon adenocarcinoma and a dependence of in vivo localization on the human colon cancer cell line used as target. This has important implications for future clinical diagnostic and therapeutic studies.     

Phase I trial of murine monoclonal antibody L6 in breast, colon, ovarian, and lung cancer

Murine monoclonal antibody (MAb) L6 binds to an antigen expressed on the surface of breast, colon, ovary, and nonsmall-cell lung cancer. This antibody effects antibody-dependent cellular cytotoxicity (ADCC) with human mononuclear cells and complement-dependent cytotoxicity (CDC) with human complement. Because of these activities, we conducted a phase I trial of MAb L6 in patients with advanced cancer. Nineteen patients whose tumors highly expressed antigen were selected for this trial. Eighteen were evaluable. MAb L6 was administered at dose levels ranging from 5 mg/m2/d to 400 mg/m2/d for 7 days and was well tolerated. The only side effects detected were fever and headaches at the highest dose levels. The serum half-life of L6 was directly related to dose and ranged from a mean of 7.7 hours at 5 mg/m2/d to 29.1 hours at 400 mg/m2/d. Peak serum concentrations ranged from 0.22 micrograms/mL to 362 micrograms/mL. Biopsies at the end of treatment showed L6 to localize well to tumor cells with apparent in vivo saturation occurring at dose levels above 100 mg/m2/d. Thirteen patients formed human antimouse antibodies (HAMA), some as early as day 13. One patient with recurrent breast cancer on the chest wall achieved a complete remission. The response was first noted at 5 weeks and a pathologic complete remission occurred at 14 weeks. Because of its favorable binding properties and the encouraging clinical effect observed, future evaluation of this MAb appears warranted.     

Antitumor effect of an anti-endothelial cell monoclonal antibody BVE-1 on solid tumor xenograft in nude mice

Thedevelopmentofnewbloodvesselsisimportantintumorgrowthandmetastasis.Targetingvascularendothelialcellstoinhibitangiogenesisoroccludethebloodvessels,blockthepassageofbloodelementstotumorcells,resultinginirreversibletumorcellsdeath,maybeanovelstrategyoftumortherapy.BurrowsFJ,etal.wasthefirstwhoproposedtheapproachofantibodyderivestargetingvascularendothelialcellsinsolidtumors.HedevelopedananimalmodelexpressingtumorvascularendotheliumbytransfectionofthetumorcellwithIFN-ygene.Whenanti-MHC-IIimm…     

Radiolocalization of xenografted human lung cancer with monoclonal antibody 8 in nude mice

A monoclonal antibody (MAb) 8 [immunoglobulin G3 (IgG3)], directed against a Mr 48,000 human lung cancer-associated antigen, was radiolabeled with either 125I or 131I, and its biodistribution was studied in nude mice bearing human lung cancer (TKB-2) over a 7-day period. 125I-labeled MAb 8 increased its binding to the tumor during the period, while the binding of 125I-labeled control IgG3 declined after initial uptake. At Day 7, percentages of injected dose of 125I-labeled MAb 8 bound to the tumor rose to 7.4%, which was a 4.4-fold increase from Day 1 and 16-fold binding of 125I-labeled control IgG3 at the same day. Tumor:blood ratios became 2.7:1 at Day 7, and tumor:liver, tumor:spleen, and tumor:kidney ratios were more than 9:1. Normal organs showed no significant uptake of 125I-labeled MAb 8, compared with those of 125I-labeled control IgG3. A clear image of the xenografted tumor was obtained at Day 5, and it further improved at Day 7, when 60% of whole body radioactivity was localized to the tumor. Autoradiography of the mouse with tumor confirmed the excellent localization of 125I-labeled MAb 8 to the tumor, although the radioactivity of the tumor was not uniformly distributed. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed that most of the radioactivity was present at the tumor in the form of degraded immunoglobulin. MAb 8 has a potential usefulness in the diagnosis and treatment of lung cancer.     

Effects of an anti-interleuktn-6 (IL-6) murine monoclonal antibody in a patient with acute monoblastic leukemia

Because IL-6 has been involved in the pathogenesis of acute monoblastic leukemia, we investigated thein vitro anti-proliferative effect and thein vivo anti-tumoral effect of an anti-IL-6 murine monoclonal antibody (mAb) in a patient with MSB type acute leukemia. In the current study, we clearly show the IL-6 dependence of monoblastic cell viability and proliferationin vitro in short-term cultures of malignant cells and the clinical activity of the anti-IL-6 murine mAb. The complete neutralization of IL-6in vivo was associated with a transient but complete disappearance of malignant monoblastic cells in the peripheral blood, with improvement or even normalization of several other biological parameters of disease activity, No immunization against the anti-IL-6 murine mAb was observed.     

Prevalence of murine mammary tumor virus antibody and antigens in normal and tumor-bearing feral mice.

Approximately 20% of normal male and female feral mice (Mus musculus) from areas with populations having either high [Lake Casitas (LC) and La Puente] or low (Bouquet Canyon) spontaneous lymphoma incidence expressed murine mammary tumor virus (MuMTV) gp52 in specific tissues. Sera from a low percentage (6%) of mice from the same trapping areas contained precipitating antibody specific for MuMTV. Although moderate to high levels of MuMTV gp52 were expressed in mammary tumor tissues of 3 of 7 LC mice and 3 of 3 (C57BL/10ScSn X LC)F1 mice, the same animals showed no detectable MuMTV-precipitating antibody. Neither MuMTV antibody nor tumor-associated MuMTV gp52 was defected in 10 LC mice bearing lymphomas or in 5 LC mice bearing hepatomas. Low levels of MuMTV gp52 expression and MuMTV antibody were also detected in subspecies of M. musculus and in the more distantly related species M. cervicolar. Compared with normal and tumor-bearing inbred mice of high (C3H/HeN) and low (C3H/HeN foster-nursed on NIH Swiss) mammary tumor strains, normal and tumor-bearing feral mice express MuMTV gp52 and MuMTV-precipitating antibodies at low frequency.     

Radioimmunotherapy of human glioma xenografts in nude mice by indium-111 labelled internalising monoclonal antibody

The potential of 111Indium (111In)-labelled internalising anti-integrin alpha 3 antibody GA17 in the radioimmunotherapy of human glioblastoma xenografts in nude mice was investigated. A radioisotope retention assay showed a rapid release of radioiodine from the glioblastoma cells after the binding of 125I-GA17, whilst 111In-GA17 was retained in the cells for a longer time period. The glioblastoma xenografts showed a high and prolonged uptake of 111In-GA17, and tumour uptake of 125I-GA17 was lower and decreased with time. In the mice which received two injections of 18.5 MBq of 111In-GA17, the growth of the subcutaneous tumour was significantly suppressed compared with the untreated group and mice injected with an 111In-labelled control antibody. These results indicate that GA17 was internalized into the glioblastoma cells and that 111In was retained within the cancer cells. The injection of a high-dose of 111In-GA17 can suppress the growth of tumour xenografts in nude mice.     

Pharmacokinetics, biodistribution, and gamma camera imaging of 111In-KC-4G3 murine monoclonal antibody in athymic nude mice with or without human tumor xenografts

The pharmacokinetics and tissue distribution of the monoclonal antibody radioconjugate 111In-diethylenetriaminepentaacetic acid-KC-4G3, which is directed against a high molecular weight mucin(s) antigen expressed on the human milk fat globule and many epithelial cell membranes, were examined in BALB/c nude mice with and without xenografts of the human tumor lines ZR-75 (mammary adenocarcinoma, KC-4G3 antigen positive) and BALL-1 (B-cell lymphoma, KC-4G3 antigen negative). Plasma of ZR-75 and BALL-1 tumor-bearing nude mice inoculated with 111In-KC-4G3 had a higher initial volume of distribution (V1), steady state volume of distribution (Vss), and plasma clearance and a lower initial half-life (t1/2 alpha) than non-tumor-bearing nude mice. There were no significant differences in biological half-life (t1/2 beta) in tumor- and non-tumor-bearing nude mice. Urinary and fecal excretion of radioactivity by ZR-75 tumor-bearing mice was greater than that of BALL-1 and non-tumor-bearing mice. Localization of 111In-KC-4G3 in mice bearing xenografts of ZR-75 was significantly greater than in mice with BALL-1 tumors. Uptake of 111In-KC-4G3 by ZR-75 tumors averaged 14% of injected dose/g at 72 h after inoculation and was unaffected by antibody dose. Significantly, the radioconjugate concentration in ZR-75 tumors remained relatively constant from 72 to 336 h post-inoculation, while that in normal tissues declined considerably over this period. Nonspecific reticuloendothelial tissue uptake of 111In-KC-4G3 was only moderately affected by pretreatment with a large excess of unlabeled normal mouse immunoglobulin and was not changed by treatment with asialofetuin. Further enhancement of specific localization of 111In-KC-4G3 was obtained by subtraction of the blood pool identified by co-inoculation of 131I-labeled, isotype-identical, normal mouse immunoglobulin. Gamma camera images of 111In-KC-4G3-inoculated ZR-75 tumor-bearing mice showed enhanced tumor localization compared to mice with BALL-1 tumors. The results of this study suggest that 111In-KC-4G3 may prove useful for imaging and possibly therapy of human malignancies expressing the high molecular weight epithelial mucin(s).     

抗Ⅳ型胶原酶单抗在人肺癌裸鼠移植模型中的免疫显像

背景与目的：基质金属蛋白酶(matrix metalloproteinases,MMPs)在肿瘤生长和转移的多个环节发挥着重要作用,Ⅳ型胶原酶作为MMPs家族的重要成员之一已成为肿瘤研究的新靶点。本文通过荷瘤裸鼠的显像实验,评价抗Ⅳ型胶原酶单克隆抗体3G11的体内特异性分布。方法：用lodogen法将^131I或^125I标记亲和纯化的单抗3G11,ELISA检测标记前后单抗的活性变化。^131I-3G11在3种不同体系(生理盐水,小牛血清,裸鼠血清)中37℃温育,检测体外稳定性。每只正常BALB／c小鼠静脉注入388．5kBq ^125-I3G11,测定单抗的药动学指标。建立人高转移PG肺癌细胞移植肿瘤模型的BALB/c(nu/nu)裸鼠每只静脉注入6．44MBq ^131I-3G11,进行免疫显像。结果：单抗3G11经亲和纯化后纯度大于98％,碘标记使单抗活性降低10％～20％。单抗3G11的体内代谢呈二室模型分布,T1/2α为7．2h,T1/2β为345．2h。^131I-3G11标记物体外72h能基本保持稳定,在荷瘤裸鼠体内72h显像清晰,至120h效果更明显。结论：显像实验证明单抗3G11对肿瘤组织有较好的特异性和亲和性。     

MCF-7荷瘤裸鼠不同树突状细胞亚群凋亡的研究

目的:通过建立MCF-7荷瘤裸鼠模型,研究树突状细胞(DCs)不同亚群的凋亡,为设计新的免疫治疗方法和新的疫苗提供详尽信息。方法:建立MCF-7裸鼠模型,随机分为荷瘤组和对照组,肿块达5 mm后处死裸鼠,取骨髓单个核细胞进行DCs诱导、分化,流式细胞仪上检测表面分子标志CD86、CD83、MHC-Ⅱ及CD34,AnnexinⅤ检测CD11c及CD123了解DCs亚群的凋亡率。结果:骨髓起源单个核细胞培养至第9天出现典型DCs形态特征,荷瘤组和对照组细胞均高表达CD86、CD83及MHC-Ⅱ,而CD34表达两组均较低。荷瘤组CD11c+CD123-细胞为(52.01±1.43)%,对照组为(56.36±1.76)%;CD123+CD11c-细胞荷瘤组为(32.19±1.71)%,对照组为(28.95±1.39)%。荷瘤组mDC凋亡率为(23.64±2.43)%,较对照组(20.05±2.49)%高,P<0.05。荷瘤组小鼠pDC凋亡率为(11.53±2.92)%,较对照组(14.96±2.96)%低,P<0.05。结论:MCF-7乳腺癌小鼠体内DCs存在mDC和pDC两种亚型,mDC凋亡率增加,使诱导Th1免疫反应能力减低;而pDC凋亡率减少,诱导体内免疫耐受的发生,机体抗肿瘤免疫反应能力因而下降。     

CXCR4单克隆抗体抑制乳腺癌MCF-7细胞裸鼠移植瘤的实验研究

目的：研究CXC趋化因子受体4（CXC chemokine receptor 4,CXCR4）单克隆抗体（CXCR4 mAb）对人乳腺癌MCF-7细胞裸鼠皮下移植瘤生长的影响,并初步探讨CXCR4 mAb抗肿瘤的作用机制。方法：采用8周龄Balb/c雌性裸鼠,建立乳腺癌MCF-7细胞裸鼠皮下移植瘤模型。运用CXCR4 mAb进行干预,从整体水平观察CXCR4 mAb对肿瘤生长的影响,采用免疫组织化学法检测肿瘤组织中增殖细胞核抗原（PCNA）、半胱氨酸天冬氨酸酶3（Caspase-3）和血管内皮细胞生长因子（VEGF）的表达情况。结果：CXCR4 mAb可明显抑制移植瘤的生长,瘤体抑制率达到71.4%;CXCR4 mAb治疗后的肿瘤组织中PCNA和VEGF表达明显下降,而Caspase-3表达上升。结论：CXCR4 mAb可能是通过抑制肿瘤细胞增殖、促进肿瘤细胞凋亡及抑制肿瘤血管形成而发挥抗肿瘤生长的作用。     

RADIOIMMUNOLOCALIZATION OF XENOGRAFTED HUMAN GASTRIC ADENOCARCINOMA WITH ~(131)I-LABELED MONOCLONAL ANTIBODY RWS_(4) IN NUDE MICE

The monoclonal antibody (MAb) RWS4 specific to membrane-associated antigen of human gastric adenocarcinoma was purified by protein A-Sepharose 4B affinity chromatography and labeled with 131I by chloramine-T method. 131-RWS,, was injected (65 μCi/10μg/0.2 ml, intraperitoneally) into the stomach cancer-bearing nude mice (solid tumor about 1 cm in diameter), and its biodistribution was studied by SPECT and gamma-counter over a peroid of 7 days. A clear image of transplanted tumor was observed on the 4th day, and the image became more clear on the 6th day. After SPECT scanning, the animals were killed on the 3rd to 7th day separately and radioactivity was detected in various organs. The ratios of T/NT were calculated. The results were shown as follows: tumor/blood, was 3.41±0.29 on the 6th day and the tumor/other organs (liver, spleen, stomach, lung, heart, kidney and brain etc.) were>3. The specificity of the 131I-RWS4 was 7.74±0.65.     

CXCR4单克隆抗体抑制乳腺癌MCF-7细胞裸鼠移植瘤的实验研究

目的 研究CXC趋化因子受体4(CXC chemokine receptor 4,CXCR4)单克隆抗体(CXCR4 mAb)对人乳腺癌MCF-7细胞裸鼠皮下移植瘤生长的影响,并初步探讨CXCR4 mAb抗肿瘤的作用机制.方法 采用8周龄Balb/c雌性裸鼠,建立乳腺癌MCF-7细胞裸鼠皮下移植瘤模型.运用CXCR4 mAb进行干预,从整体水平观察CXCR4 mAb对肿瘤生长的影响,采用免疫组织化学法检测肿瘤组织中增殖细胞核抗原(PCNA)、半胱氨酸天冬氨酸酶3(Caspase-3)和血管内皮细胞生长因子(VEGF)的表达情况.结果 CXCR4 mAb可明显抑制移植瘤的生长,瘤体抑制率达到71.4%;CXCR4 mAb治疗后的肿瘤组织中PCNA和VEGF表达明显下降,而Caspase-3表达上升.结论 CXCR4 mAb可能是通过抑制肿瘤细胞增殖、促进肿瘤细胞凋亡及抑制肿瘤血管形成而发挥抗肿瘤生长的作用.