EB病毒转化Hu－TLC－SCID小鼠脾细胞的实验研究

利用ＥＢ病毒转化可产生较高水平人ＩｇＧ和特异性抗２型登革病毒人抗体的Ｈｕ－ＴＬＣ－ＳＣＩＤ小鼠脾细胞,通过免疫组化、免疫荧光和ＰＣＲ法检测转化细胞的人Ｂ细胞表面标志、ＥＢ病毒抗原和ＥＢ病毒基因。结果表明,被转化的Ｈｕ－ＴＬＣ－ＳＣＩＤ小鼠脾细胞能继续产生抗２型登革病毒的特异性人抗体,并具有人Ｂ细胞的、ＳｍＩｇＧ标志及ＥＢ病毒潜伏膜蛋白－１（ＬＭＰ－１）基因,可表达ＬＭＰ－１和ＥＢ病毒核抗原（ＥＢＮＡ）。     

Growth of MCF-7 human breast carcinoma in severe combined immunodeficient mice: Growth suppression by recombinant interleukin-2 treatment and role of lymphokine-activated killer cells

Summary The severe combined immunodeficient (SCID) mouse, lacking functional T and B lymphocytes, has been considered by many groups to be a prime candidate for the reconstitution of a human immune system in a laboratory animal. In addition, this immuno-deficient animal would appear to have excellent potential as a host for transplanted human cancers, thus providing an exceptional opportunity for the study of interactions between the human immune system and human cancer in a laboratory animal. However, because this animal model is very recent, few studies have been reported documenting the capability of these mice to accept human cancers, and whether or not the residual immune cells in these mice (e.g. natural killer, NK, cells; macrophages) possess antitumor activities toward human cancers. Thus, the purpose of this study was (a) to determine whether or not a human breast carcinoma cell line (MCF-7) can be successfully transplanted to SCID mice, (b) to determine whether or not chronic treatment of SCID mice with a potent lymphokine (recombinant interleukin-2, rIL-2) could alter MCF-7 carcinoma growth, and (c) to assess whether or not rIL-2-activated NK cells (LAK cells) are important modulators of growth of MCF-7 cells in SCID mice. To fulfill these objectives, female SCID mice were implanted s.c. with MCF-7 cells (5 × 10⁶ cells/mouse) at 6 weeks of age. Six weeks later, some of the mice were injected i.p. twice weekly with rIL-2 (1 × 10⁴ U mouse^–1 injection^–1). Results clearly show that MCF-7 cells can grow progressively in SCID mice; 100% of the SCID mice implanted with MCF-7 cells developed palpable measurable tumors within 5–6 weeks after tumor cell inoculation. In addition, MCF-7 tumor growth was significantly (P <0.01) suppressed by rIL-2 treatment. rIL-2 treatment was non-toxic and no effect of treatment on body weight gains was observed. For non-tumor-bearing SCID mice, splenocytes treated in vitro with rIL-2 (lymphokine-activated killer, LAK, cells) or splenocytes derived from rIL-2-treated SCID mice (LAK cells) had significant (P <0.01) cytolytic activity toward MCF-7 carcinoma cells in vitro. In contrast, splenocytes (LAK cells) derived from tumor(MCF-7)-bearing rIL-2-treated SCID mice lacked cytolytic activities toward MCF-7 cells in vitro. No significant concentration of LAK cells in MCF-7 human breast carcinomas was observed nor did rIL-2 treatment significantly alter growth of MCF-7 cells in vitro. Thus, while rIL-2 treatment significantly suppressed growth of MCF-7 breast carcinomas in SCID mice, the mechanism of this growth suppression, albeit clearly not involving T and B lymphocytes, does not appear to be mediated via a direct cytolytic activity of LAK cells toward the carcinoma cells. However, rIL-2-activated SCID mouse splenocytes (LAK cells) do possess the capability of significant cytolytic activity toward MCF-7 human breast carcinoma cells. Thus, treatment of SCID mice with a potent lymphokine (rIL-2) induces a significant antitumor host response, a response that does not involve T and B lymphocytes and appears not to involve NK/LAK cells. This host response must be considered in future studies designed to investigate the interactions of reconstituted human immune systems and human cancers within this highly promising immuno deficient experimental animal model.     

hu-PBL-SCID小鼠体内人淋巴细胞状况及其对人肺癌移植瘤转移的影响

将人外周血淋巴细胞经腹腔移植于T、B细胞严重联合免疫缺陷的SCID小鼠后,成功地建立了hu - PBL- SCID小鼠模型。在移植后4 周,其小鼠血清中存在人免疫球蛋白,其脾淋巴细胞中,所检测的8 种免疫表型人淋巴细胞亚群均存在,表明人淋巴细胞在SCID小鼠体内出现了增殖或重建。但hu- PBL- SCID小鼠及未免疫重建的SCID小鼠体内人肺巨细胞癌PLA- 801DL的生长及转移情况未见明显差异,提示hu- PBL- SCID小鼠体内的人淋巴细胞不具有明显的抗肿瘤活性。     

Utility of immunodeficient mouse models for characterizing the preclinical pharmacokinetics of immunogenic antibody therapeutics

Prior to clinical studies, the pharmacokinetics (PK) of antibody-based therapeutics are characterized in preclinical species; however, those species can elicit immunogenic responses that can lead to an inaccurate estimation of PK parameters. Immunodeficient (SCID) transgenic hFcRn and C57BL/6 mice were used to characterize the PK of three antibodies that were previously shown to be immunogenic in mice and cynomolgus monkeys. Four mouse strains, Tg32 hFcRn SCID, Tg32 hFcRn, SCID and C57BL/6, were administered adalimumab (Humira®), mAbX and mAbX-YTE at 1 mg/kg, and in SCID strains there was no incidence of immunogenicity. In non-SCID strains, drug-clearing ADAs appeared after 4–7 days, which affected the ability to accurately calculate PK parameters. Single species allometric scaling of PK data for Humira® in SCID and hFcRn SCID mice resulted in improved human PK predictions compared to C57BL/6 mice. Thus, the SCID mouse model was demonstrated to be a useful tool for assessing the preclinical PK of immunogenic therapeutics.     

Enhanced Engraftment of HTLV-I-Infected Human T Cells in Severe Combined Immunodeficiency Mice by Anti-asialo GM-1 Antibody Treatment

The effects of anti-asialo GM-1 antibody (AAGM) treatment on the engraftment of human T-cell leukemia virus type I (HTLV-I)-infected human T cells in severe combined immunodeficiency (SCID) mice were studied. The frequency of tumor formation in an HTLV-I-transformed human T-cell line, MT-2 cells, at the site of inoculation was significantly higher in AAGM-treated than untreated mice (P<0.05): 16/18 (89%) and 16/26 (62%), respectively. The promotive effect of AAGM treatment on tumor development was marked in the early stage (less than 3 weeks), suggesting that the immediate reaction of natural killers to the inoculated cells may be important for the prevention of tumor development. The surface phenotypes and clonality of the tumor cells were the same as the MT-2 cells inoculated. Inoculation of peripheral blood mononuclear cells (PBMC) from one of the 4 adult T-cell leukemia/lymphoma (ATL) patients resulted in the development of tumors in AAGM-treated SCID mice. However, the surface phenotypes of the cells from these tumors were a mixture of B cells and T cells, suggesting that these tumors consisted of Epstein-Barr virus-transformed B cells and HTLV-I-transformed T cells. In addition, HTLV-I was detected by polymerase chain reaction in various organs of the mice inoculated with PBMC from the ATL patient and the asymptomatic carrier examined. These results suggest that elimination of natural killer function by AAGM treatment is important, although such treatment is not always necessary for the engraftment of HTLV-I-infected cells in SCID mice.     

Providing a microenvironment for the development of human CD34+ hematopoietic cells in SCID mice

In order to develop a convenient small-animal model that can support the differentiation of human bone-marrow-derived CD34+ cells, we transplanted SCID mice with an immortalized human stromal cell line, Lof(11–10). The Lof(11–10) cell line has been characterized to produce human cytokines capable of supporting primitive human hematopoietic cell proliferation in vitro. Intraperitoneal injection of Lof(11–10) cells into irradiated SCID mice by itself resulted in a dose-dependent survival of the mice from lethal irradiation. The radioprotective survival was reflected by an increase in the growth and number of mouse bone-marrow-derived committed hematopoietic progenitors. The Lof(11–10) cells localized to the spleen, but not to the bone marrow of these animals and resulted in detectable levels of circulating human IL-6 in their plasma. Secondary intravenous injections of either human or simian CD34+ cells into the Lof(11–10)-transplanted SCID mice resulted in engraftment of injected cells within the bone marrow of these mice. The utility of this small-animal model that allows the growth and differentiation of human CD34+ cells and its potential use in clinical gene therapy protocols are discussed.     

荷瘤SCID-hu鼠模型及其肿瘤实验研究现状

严重联合免疫缺陷鼠（severe combined immune deficiency mice,SCID）具有T、B淋巴细胞联合免疫缺陷等生物学特性,可以将人类有关免疫细胞、免疫组织和器官移植入其体内进行人免疫功能重建-SCID-hu鼠。荷瘤SCID-hu鼠模型为人类肿瘤的发病机制、生物治疗等方面的研究提供了良好的实验平台。     

NOD/SCID小鼠模型在实验血液学研究中的应用

NOD/SCID（非肥胖糖尿病/重症联合免疫缺陷）小鼠是在SCID（重症联合免疫缺陷）小鼠的基础上与非肥胖性糖尿病小鼠（NOD/Lt）品系回交的免疫缺陷鼠。NOD/SCID小鼠既有先天免疫缺陷,又有T和B淋巴细胞缺乏,各种肿瘤细胞可以植入,且较少发生排斥反应及移植物抗宿主病（GVHD）,所以NOD/SCID小鼠逐渐成为血液学实验研究的有用工具。本文从NOD/SCID小鼠的生物学特性、建立人类白血病模型、干细胞移植、药物研究及NOD/SCID小鼠应用中存在的不足和改良等方面综合述评。     

Identical TCR beta-chain rearrangements in streptococcal angina and skin lesions of patients with psoriasis vulgaris

Tonsillar infection with Streptococcus pyogenes may induce several nonsuppurative autoimmune sequelae. The precise pathogenetic mechanisms behind this clinically well-established association are still unresolved. Using TCR analysis, we sought to identify a link between streptococcal tonsillitis and the T cell-mediated autoimmune response in psoriasis. Three patients with streptococcal-induced psoriasis underwent tonsillectomy. Using size spectratyping and sequencing of TCR beta-chain variable region gene (TCRBV) rearrangements, we compared the TCR usage of psoriatic skin lesions, blood, tonsils, and tonsillar T cells fractionated according to the expression of the skin address in "cutaneous lymphocyte-associated Ag" (CLA). TCRBV-size spectratype analysis of the blood lymphocytes, tonsils, and the CLA-negative tonsillar T cells revealed largely unselected T cell populations. Instead, TCRBV gene families of the psoriatic lesions and skin-homing CLA-positive tonsillar T cells displayed highly restricted spectratypes. Sequencing of TCRBV cDNA identified various clonal TCRBV rearrangements within the psoriatic lesions that indicated Ag-driven T cell expansion. Several of these clonotypes were also detected within the tonsils and, in one of the patients, within the small subset of CLA-positive tonsillar T cells, suggesting that T cells from the same T cell clones were simultaneously present within skin and tonsillar tissue. Because after tonsillectomy psoriasis cleared in all three patients our observations indicate that T cells may connect psoriatic inflammation to streptococcal angina. They suggest that the chronic streptococcal immune stimulus within the tonsils could act as a source for pathogenic T cells in poststreptococcal disorders, and they may help to explain why eliminating this source with tonsillectomy may improve streptococcal-induced sequelae.     

急性髓性白血病SCID小鼠模型的建立及鉴定

目的:探讨建立急性髓性白血病小鼠模型,并对模型建立过程进行观察、分析和鉴定.方法:重症联合免疫缺陷小鼠(SCID)建立HL-60细胞白血病动物模型,观察SCID小鼠一般情况,监测小鼠外周血HL-60细胞、白细胞、红细胞、血小板的变化,用流式细胞术、骨髓染色体检查等检测小鼠骨髓,濒死或死亡小鼠行组织病理学检查.结果:接种后3-5周,外周血白细胞上升,外周HL-60细胞占非红系有核细胞比例为3%-11%.骨髓HL-60细胞占非红系有核细胞中比例为40%-58%,骨髓细胞中CD33抗原阳性率8.18%-24.45%.小鼠骨髓细胞中有中、亚中部着丝点染色体.结论:HL-60细胞静脉接种SCID小鼠,白血病发病率为100%.其发病症状及组织浸润与人类白血病相类似,可用于研究白血病增殖、分化等机制,是探索新的白血病治疗手段及判断患者预后的重要载体.     

免疫重建荷人膀胱癌-SCID鼠模型的建立

目的：探讨建立稳定的荷人膀胱癌SCID 鼠人化复合模型的方法,为在人免疫重建荷人膀胱肿瘤SCID 鼠模型检测重组BCG 的免疫刺激和免疫保护中打下基础。方法：经SCID 鼠腹腔内注射人PBL、皮下接种RT4 膀胱癌细胞,于接种后4 周检测SCID 鼠体内人免疫细咆水平（IgG 和CD^3＋、CD^4＋、CD^8＋ T 细胞）及脾脏重量,观察皮下成瘤潜伏期及成瘤率。结果：模型组100％成瘤,病理类型为移行细胞癌;检测SCID 鼠血中人IgG 均一定水平存在,与对照组间差异有统计学意义（P〈0.01）;人CD^3＋、CD^4＋、CD^8＋T 细胞在鼠血及脾中均有表达,而对照组均未检出（P〈0.05）;4 周鼠脾重平均（178.9± 45.2）mg。较对照组（40.6± 14.8）mg 差异有统计学意义（P〈0.01）。结论：采用腹腔注射人PBL、皮下接种RT4膀胱癌细胞的方法可以有效地建立人化荷人膀胱癌SCID 鼠模型,较好地模拟人浸润性膀胱癌体内生物学特性,是膀胱癌免疫基因治疗的较理想模型。     

The Role of Selectins and CD18 in Leukotriene B4-Mediated White Blood Cell Emigration in Human Skin Grafts Transplanted on SCID Mice

The purpose of this study was to examine the role of selectins and CD18 cell adhesion molecules (CAMs) in inflammation induced by injection of leukotriene B₄(LTB₄) into human skin. To accomplish this, the expression of CAMs and the ability of specific antibodies against CAMs to block white blood cell (WBC) transmigration were studied in an in vivo model consisting of human skin transplanted onto mice with the severe combined immune deficiency (SCID) mutation. The results indicate that LTB₄-induced WBC transmigration in the human/SCID model is rapid and pronounced; however, it is not accompanied by a significant upregulation of the baseline expression of endothelial P-selectin, E-selectin, ICAM-1 or VCAM-1. An anti-murine CD18 mAb markedly inhibited white cell infiltration (89% inhibition) confirming the importance of β₂integrins in the process. The role of selectins was also examined. MEL-14, a bioactive antibody against murine L-selectin inhibited transmigration by 66%. A significant, but smaller, effect (39% inhibition) was observed by blocking E-selectin function. These results indicate that LTB₄-induced inflammation does not require upregulation of endothelial CAM expression and, in contrast to TNFα-induced transmigration, is only partially blocked by anti-E-selectin antibodies.     

人T细胞急性淋巴细胞白血病小鼠动物模型的建立

目的:通过建立一理想的动物模型来模拟T细胞急性淋巴细胞白血病的发病状态,为探索急性淋巴细胞白血病全新的治疗方法提供平台。方法:采用抗鼠-CD122抗体注射NOD/SCID小鼠进行预处理,通过尾静脉注射9例不同病例的白血病细胞,以及1株T-ALL细胞系。通过检测小鼠体内白血病细胞及脏器白血病细胞浸润情况,观察白血病细胞植入。将白血病细胞进行二次移植,观察移植稳定性。对白血病动物模型进行药物处理,观察小鼠生存期,模拟人体治疗反应。结果:有4例病例的细胞及T-ALL细胞株成功植入。流式细胞检测显示受体小鼠体内较多比例人CD45+细胞表达,免疫组化显示CD45+细胞浸润小鼠不同脏器,系列移植也获得成功。体内药物处理显示地塞米松能延长小鼠的生存期,与临床观察相一致。结论:成功建立经抗鼠CD122单抗预处理的人T细胞急性淋巴细胞白血病NOD/SCID小鼠模型,具有原发疾病的所有主要特征。     

急性淋巴细胞白血病CD34+CD38-细胞在NOD/SCID小鼠体内的自我更新与增值能力

目的 探索急性淋巴细胞白血病(ALL)患者CD34+ CD38-细胞移植到NOD/SCID小鼠体内建立白血病的可行性、自我更新与增殖潜能.方法 分选并鉴定ALL患者骨髓CD34+ CD38-细胞及对照CD34- CD38+细胞后,经尾静脉分别注射104个细胞于亚致死剂量射线照射的NOD/SCID小鼠体内,连续监测小鼠状态以及外周血血象改变,对濒死或死亡小鼠进行骨髓检查、肝脾病理学检查.结果 接种从ALL患者分选的CD34+ CD38-细胞到NOD/SCID小鼠体内后4周,小鼠外周血白细胞上升,到8周左右达高峰,约15×109～20× 109/L,原始及幼稚淋巴细胞明显增多.骨髓象显示以原始及幼稚淋巴细胞增生为主,约为40％,且肝脾组织也有白细胞浸润,明显高于接种了对照组CD34- CD38+细胞的NOD/SCID小鼠.结论 ALL患者CD34+CD38-细胞可以成功移植NOD/SCID 小鼠,在小鼠体内增殖形成白血病,说明该群细胞具有自我更新和增殖的潜能,可作为探索白血病起始细胞研究的重要载体.     

Immunotoxin studies in a model of human T-cell acute lymphoblastic leukemia developed in severe combined immune-deficient mice

The transplantation of the human T-cell acute lymphoblastic leukemia (T-ALL) cell line HSB-2 into severe combined immune-deficient (SCID) mice was found to produce a disseminated pattern of leukemia similar to that seen in humans. The iv injection of 10⁷ HSB-2 cells was associated with a universally fatal leukemia. Histopathological examination of animals revealed the spread of leukemia initially from bone marrow to involve all major organs including the meninges. An immunotoxin (HB2-Sap) was constructed by conjugating the anti-CD7 monoclonal antibody (MAb) HB2 to the ribosome inactivating protein (RIP) saporin. An in vitro protein synthesis inhibition assay revealed specific delivery of HB2-Sap immunotoxin (IT) to CD7⁺ HSB-2 target cells with an IC₅₀ of 4.5 pM. In an in vivo study, the IT was shown to significantly prolong the survival of SCID mice injected with HSB-2 cells compared to untreated control animals. This therapeutic effect was seen both with a single injection of 10 μg of IT given 7 d after the injection of HSB-2 cells, and was even more effective when IT was administered as three daily injections of 10 μg on d 7, 8, and 9. These results demonstrate the useful application of human leukemia xenografts in SCID mice and the potential therapeutic effect of an anti-CD7 IT in human T-ALL.     

EB病毒诱发人B细胞淋巴瘤的分子病理特性

EB病毒 (EBV ,Epstein Barrvirus)与人类多种肿瘤有关 ,尤其是与鼻咽癌和淋巴瘤的关系密切。为此研究了EB病毒在huPBL SCID嵌合体小鼠体内诱发人B细胞淋巴瘤的分子特性及肿瘤发生机制。从健康成人外周血分离出淋巴细胞 ,将之移植到SCID小鼠腹腔内 ,实验感染EBV ,观察肿瘤的形成 ;采用单向免疫扩散法连续监测小鼠血清中人IgG的含量。分别用PCR方法检测肿瘤组织中是否存在人Alu序列 ,原位杂交检测肿瘤组织中EB病毒小RNA分子EBER 1;免疫组织化学方法检测人白细胞分化抗原 (CD4 5、CD2 0、CD4 5RO、CD3) ,病毒基因(LMP1、EBNA2、BZLF1)的表达 ,以及细胞瘤基因蛋白 (p5 3、C myc、Bcl 2、Bax)在诱发肿瘤中的表达情况。结果发现 ,实验中 34只感染EBV的huPBL SCID小鼠有 2 4只诱发出肿瘤 ,根据病理形态学特征、Alu PCR和免疫标志均证实诱发瘤是人源性B淋巴细胞肿瘤。原位分子杂交显示肿瘤细胞核内存在EBER 1,少数瘤细胞表达EB病毒BZLF1蛋白阳性 ,部分瘤细胞表达LMP1和EBNA2蛋白阳性。连续监测 12只huPBL SCID小鼠血清中人IgG含量 ,发现IgG水平随诱瘤时间延长和肿瘤生长有逐渐增高趋势。免疫组化显示诱发的 2 4例淋巴瘤组织p5 3、C myc、Bcl 2和Bax蛋白表达阳性率分别为 83.33%、10 0 %、95 .83%、91.6 7%。结果     

Immunotherapy of human colon cancer by antibody-targeted superantigens

T lymphocytes generally fail to recognize human colon carcinomas, suggesting that the tumour is beyond reach of immunotherapy. Bacterial superantigens are the most potent known activators of human T lymphocytes and induce T cell cytotoxicity and cytokine production. In order to develop a T-cell-based therapy for colon cancer, the superantigen staphylococcal enterotoxin A (SEA) was given tumour reactivity by genetic fusion with a Fab fragment of the monoclonal antibody C242 reacting with human colon carcinomas. The C242Fab-SEA fusion protein targeted SEA-reactive T cells against MHC-class-II-negative human colon carcinoma cells in vitro at nanomolar concentrations. Treatment of disseminated human colon carcinomas growing in humanized SCID mice resulted in marked inhibition of tumour growth and the apparent cure of the animals. Therapeutic efficiency was dependent on the tumour specificity of the fusion protein and human T cells. Immunohistochemistry demonstrated massive infiltration of human T cells in C242Fab-SEA-treated tumours. The results merit further evaluation of C242Fab-SEA fusion proteins as immunotherapy in patients suffering from colon carcinoma.     

Development of antigenic heterogeneity in the splenic meshwork of severe combined immunodeficient (SCID) mice after reconstitution with T and B lymphocytes

Recently, we produced monoclonal antibodies reacting specifically with the reticular meshwork (RM) of lymphoid tissues, and demonstrated that, in the splenic white pulp of normal mouse, the antigenic heterogeneity of RM was associated with the segregation of the T and B lymphocytes. In the present study, we attempted to visualize further the interaction between splenic RM and T and B lymphocytes transferred into severe combined immunodeficient (SCID) mice. The splenic white pulp of naive SCID mice, containing a few T and B cells, showed little tendency for T-B segregation and antigenic diversity of RM. Transfer of spleen or bone marrow cells from normal mice resulted in complete recovery of lymphocyte populations, showing not only a clear segregation of T and B lymphocytes but also a remarkable antigenic diversity of RM. The same results were obtained following the transfer of spleen or bone marrow cells from the nude mouse. Next, we transferred purified T lymphocytes to one group of SCID mice and B cells to another. In mice given T cells, a few B cells were observed in the white puop; T lymphocytes lodged not only in the inner periarterial lymphatic sheath (PALS) but also in the outer PALS and follicles. In the animals to which B cells were transferred, T cells were few and the homing of B cells occurred only into their proper compartments, such as the outer PALS, follicles and marginal zone, but not in the inner PALS. Thus, B cells can home into their proper compartments of the splenic white pulp independently of T lymphocytes.     

Retroviral producer cells cause sarcoma in severe combined immunodeficiency mice

Direct in situ introduction of retroviral producer cells might provide a form of treatment for localized tumors. A possible undesirable consequence of this treatment could be uncontrolled proliferation of the injected producer cells. To test this possibility, severe combined immunodeficiency (SCID) mice were reconstituted with human peripheral blood lymphocytes which were marked with a retroviral vector using a coculture method. Although specific measures were taken to remove the possible contaminating producer cells, a high percentage of mice developed fibrosarcoma 2–6 weeks after reconstitution. We hypothesized that tumors arose from a small number of contaminating producer cells in the inoculum. Tumor cells were consistently DNA tetraploid, a characteristic of the producer cell line. DNA extracted from tumor tissue was found to contain the gene (neomycin phosphotransferase) used to mark the producer cell line. Furthermore, SCID mice injected with 1 × 10⁴ producer cells developed tumors with analogous characteristics. This report indicates that the retroviral producer cell line is tumorigenic in immune-deficient animals.     

Anti-tumor effects of fusion vaccine prepared by renal cell carcinoma 786-O cell line and peripheral blood dendritic cells of healthy volunteers in vitro and in human immune reconstituted SCID mice

Dendritic cells (DC), as professional antigen presenting cells, play the central role in the process of body initiating the anti-tumor immunity, and the study on DC anti-tumor vaccine has become heated in recent years. In this study, we used polyethylene glycol (PEG) to induce renal cell carcinoma (RCC) 786-O cell line fused with peripheral blood DC of healthy volunteers, and discuss the biological characteristics of fusion vaccine and its anti-tumor effects in vitro and in human immune reconstituted SCID mice model of RCC. The study found that PEG could effectively induce cell fusion, and the expressions of CD86 and HLA-DR in fusion vaccine group were significantly up-regulated compared with the DC control group; the secretion of IL-12 was much higher and longer than that of the control; the functions of dendritic cell-tumor fusion vaccine to stimulate the proliferation of allogenic T lymphocytes and to kill RCC786-O cells in vitro were significantly higher than those of the control group, and after the killing, apoptosis body was observed in the target cells; after the injection of fusion vaccine into human immune reconstituted SCID mice model of RCC786-O via vena caudalis, the volume of mice tumor was reduced significantly, proliferation index of tumor cells decreased obviously compared with that of the control group, and more hemorrhage and putrescence focuses presented, accompanying large quantity of lymphocytes soakage. The results of this experimental study shows that fusion vaccine of RCC786-O cell line and DC can significantly stimulate the proliferation of allogenic T cells and specifically inhibit and kill RCC cells in vitro and in vivo, which makes the DC-RCC786-O fusion vaccine a possible new way of effective RCC immunotherapy.