女性供者特征对粒细胞集落刺激因子动员的骨髓和外周血混合采集物中造血和免疫细胞组份的影响

目的 探讨女性健康供者特征对粒细胞集落刺激因子（G CSF）预激的骨髓和外周血混合采集物造血细胞和免疫细胞组份的影响。方法 111名健康女性供者应用G CSF动员,用流式细胞仪测定骨髓和外周血混合采集物中的CD34+细胞和T细胞亚群的数量,并分析怀孕、年龄、身高等供者特征对骨髓和外周血采集物中细胞组份的影响。结果 111例女性健康供者骨髓和外周血混合采集物中的CD34+细胞、CD3+T细胞、CD3+CD4+T细胞、CD3+CD8+T细胞和CD3+CD4-CD8-调节性T细胞的数量以每公斤供者体重计算的中位值分别为2.39×106/kg、226.57×106/kg、120.80×106/kg、89.99×106/kg和15.05×106/kg。①年龄对混合移植物中CD3+CD4-CD8-调节性T细胞的数量有影响。②体重指数（BMI）对混合采集物中的CD3+T细胞以及CD3+CD4-CD8-T细胞的数量有影响;③外周血干细胞采集当天的淋巴细胞（LYM）对混合采集物中的CD3+T细胞、CD3+CD4+T细胞和CD3+CD8+T细胞的数量有影响;④骨髓干细胞采集当天的LYM对混合采集物中CD3+T细胞和CD3+CD4-CD8-调节性T细胞的数量有影响;⑤与怀孕供者相比,未怀孕供者混合采集物中含有更高数量的CD3+CD8+ T细胞。结论 供者年龄、BMI、是否怀孕以及骨髓干细胞和外周血干细胞采集当天的LYM是骨髓免疫组份的主要影响因素。     

特异诱导脐血CD8+抗白血病细胞毒淋巴细胞的研究

微小残留病灶(minimal residual disease,MRD)的存在是导致白血病复发的主要根源,特异性免疫治疗能有效地清除MRD,其中的策略之一就是诱导并回输白血病特异性的细胞毒性T淋巴细胞(cytotoxic T lymphocyte,CTL).本实验的目的是研究脐血能否在体外诱导生成CD8+ CTL,所生成的CD8+ CTL能否特异性杀伤白血病细胞,从而确定脐血淋巴细胞的利用价值及用于特异性免疫治疗的可行性.通过联合细胞因子体外诱导脐血单个核细胞(mononuclear cells,MNC)分化为树突状细胞(dendritic cells,DC),同时负载U937冻融抗原;成熟DC刺激同源的脐血T淋巴细胞成为CTL,经MACS磁珠分选出CD8+ CTL.用倒置显微镜、扫描电镜及流式细胞仪等方法检测DC,四甲基偶氮唑蓝(methyl thiazolyl tetrazolium,MTT)法测定杀伤活性.结果显示,10份人脐血标本均可培养出形态典型、功能成熟的DC.3组效应细胞CD8+ CTL、CD8- CTL和T淋巴细胞(TL)组在相同效靶比(40∶1)对U937细胞株的杀伤率分别为(66.36±12.43)%、(34.47±8.19)%和(15.79±4.64)%,以CD8+ CTL组最高;效靶比为40∶1时,CD8+ CTL对U937细胞株的杀伤率(66.36%)高于对K562细胞株的杀伤率(41.97%)(P＜0.05);而CD8- CTL对U937细胞株和K562细胞株的杀伤率无显著差异(P＞0.05).结论用负载U937白血病细胞株抗原的成熟脐血DC可使脐血淋巴细胞诱导产生特异性的CD8+ CTL;CD8+ CTL对U937白血病细胞株的杀伤活性强于CD8- CTL的作用;CD8+ CTL对U937白血病细胞株杀伤具有特异性.     

HLA-A~*0201/WT1五聚体联合胞内IFNγ染色在检测白血病患者外周血WT1特异性T细胞中的应用

本研究探讨五聚体及胞内因子染色在定性定量检测抗原特异性T细胞中的应用价值。用RT-PCR方法检测受试者WT1表达水平;用HLA-A*0201/WT1五聚体及胞内IFNγ染色检测14例表达HLA-A*0201的白血病患者全相合移植前后及其供者外周血中的WT1特异性T细胞。结果表明:14例供者中2例有低水平WT1表达,白血病患者均有不同水平的WT1表达。14例供者均未检测到WT1+CD8+CTL和WT1+IFNγ+细胞;移植前14例患者中2例可检出WT1+CD8+CTL,3例检出WT1+IFNγ+细胞,二者间无明显差异(p=0.357),而移植后均可检出WT1+CD8+CTL和WT1+IFNγ+细胞,明显高于移植前(p值均0.01)。移植后大部分患者均在30天内检出WT1+CD8+CTL和WT1+IFNγ+细胞,但后者检出率高于前者(p=0.014)。14例患者中WT1+CD8+CTL峰值中位数为0.18%,而WT1+IFNγ+细胞峰值中位数为0.83%,明显高于前者(p=0.005);WT1+CD8+CTL峰值中位时间为移植后75天,WT1+IFNγ+细胞峰值中位时间为移植后105天,但二者间无明显差异(p=0.455)。结论:五聚体及胞内IFNγ染色能有效检测白血病患者外周血中白血病抗原特异性T细胞;两种方法联合检测有助于抗原特异性T细胞的准确定性定量检测。     

特异诱导脐血CD8+抗白血病细胞毒淋巴细胞的研究

目的研究体外诱导脐血CD8+细胞毒性T淋巴细胞(CTL)特异性杀伤白血病细胞的作用,探讨脐血淋巴细胞用于特异性免疫治疗的可行性.方法联合细胞因子体外诱导10份脐血单个核细胞(MNC)分化为树突细胞(DC),同时负载U937冻融抗原;成熟DC刺激同源的脐血T淋巴细胞成为CTL,经MACS磁珠分选出CD8+CTL.倒置显微镜、扫描电子显微镜及流式细胞术等方法检测DC细胞特性.MTT法测定细胞杀伤活性.结果10份脐血标本均可培养出形态典型、功能成熟的DC.CD8+CTL、CD8-CTL和淋巴细胞(TL)组对U937细胞不同效靶比的杀伤率以CD8+CTL组最高;CD8+CTL在401效靶比时对靶细胞U937细胞的杀伤率高于对K562细胞的杀伤率[分别为(66.36±12.43)%和(41.97±14.24)%,(P《0.05)];而CD8-CTL在401效靶比时对U937细胞和K562细胞的杀伤率差异无统计学意义[分别为(34.47±8.19)%和(22.45±4.00)%(P》0.05)].结论用负载U937细胞抗原的成熟脐血DC,诱导出脐血淋巴细胞特异性的CD8+CTL;CD8+CTL对U937细胞的杀伤活性强于CD8-CTL;CD8+CTL对U937细胞的杀伤活性具有特异性.     

调节性T细胞与异基因造血干细胞移植中的移植物抗宿主病

移植物抗宿主病(GVHD)是异基因造血干细胞移植供者移植物中T细胞识别不同的异基因受者抗原导致的复杂疾病过程,移植物T细胞去除却影响植入、免疫抑制、失去移植物抗白血病作用.CD4+CD25+调T细胞(Tregs)在控制自身免疫性疾病中具有重要意义,在控制异源反应性免疫应答中也起重要作用.Tregs预防GVHD机制是抑制普通T细胞(Tcons)增殖与功能活性.本文主要对CD4+CD25+Tregs调控GVHD及免疫治疗现状及应用前景作一综述.     

rhG-CSF对健康供者T细胞CCR5表达的不同调控及其与急性移植物抗宿主病的相关性研究

探讨重组人粒细胞集落刺激因子(rhG-CSF)对健康供者T细胞趋化因子受体CCR5表达的影响及其与急性移植物抗宿主病(aGVHD)的相关性,从而了解rhG-CSF动员在异基因造血干细胞移植(allo-HSCT)后诱导免疫耐受的机制。选取68名亲缘allo-HSCT健康供者及相应的68例受者为研究对象,应用流式细胞技术测定健康供者rhG-CSF动员前后外周血CD4+和/CD8+T细胞表面CCR5的表达,比较其变化。根据动员前后供者外周血CD4+/CD8+T细胞表面CCR5的表达变化情况,将其中可供分析的62例供者分为表达下调组和未下调组,比较两组受者II-IV度aGVHD的累计发生率。结果表明,与动员前外周血相比,rhG-CSF动员后的外周血中CD4+和CD8+T细胞表面CCR5表达均值无明显变化,但在不同个体之间表现出明显的不一致性。34例(50%)供者CD4+细胞CCR5表达下调,50%表达不变或上调,而42例(61.8%)供者CD8+T细胞CCR5表达下调,26例(38.3%)供者CCR5表达不变或上调。分析可供评价的62例移植患者表明,供者CD4+T细胞CCR5下调组受者II-IV度aGVHD发生率较未下调组明显降低(16.6%vs 43.3%,P=0.032),而CD8+T细胞CCR5下调组受者II-IV度aGVHD的累计发生率较未下调组呈现增高趋势(37.8%vs 16.0%,P=0.065)。结论:rhG-CSF动员影响T细胞表面CCR5的表达,而这些作用可能影响T细胞体内迁移行为,减少T细胞向GVHD靶器官聚集,从而降低allo-HSCT后aGVHD的发生率。     

供者凋亡细胞静脉输注在异种肝移植中所产生体液免疫机理

目的以贵州香猪为供者、中国猕猴为受体的异种肝移植模型,采用静脉输注异种异基因骨髓及凋亡细胞的方法预处理受体,研究凋亡细胞对异种肝脏移植免疫排斥反应的影响,探讨异种肝脏移植免疫耐受的机制。方法受者猕猴随机分为A、B、C组,A组为阴性对照组,n=6;B组为实验对照组,n=28,在接受RIC之后,再接受供者贵州香猪的异种异基因骨髓(BM)静脉输注;C组为实验组,n=36,在接受RIC之后,再接受供者贵州香猪的BM和凋亡细胞同时静脉输注。观察各组受体的生存期,检测受体术后外周血中ALT、TB含量、Foxp3+CD4+CD25+调节性T细胞和T细胞亚群上GITR的表达,检测受体术后第14天移植肝的病理变化和术后第14天受体脾脏CTL杀伤活性。结果C组肝移植术后经历短暂排斥反应,最终可获免疫耐受并长期存活,其外周血中Foxp3+CD4+CD25+调节性T细胞表达比例在术后第14天渐恢复正常,受体外周血中CD3+CD4+T细胞上GITR表达降低,CD3+CD8+T细胞上GITR表达增加,提高CTL的杀伤活性;B组受体在术后第17~2 1天死亡,与A、C组相比,外周血血清中ALT、TB含量明显升高,而Foxp3+CD4+CD25+调节性T细胞比例明显降低。结论供者凋亡细胞静脉输注在异种肝移植中所产生体液免疫耐受的机理,可能是通过诱导受体外周血中CD3+CD4+T细胞上GITR表达降低,CD3+CD8+T细胞上GITR表达增加,提高CTL的杀伤活性来实现的。     

异基因造血干细胞移植健康供者外周血干细胞二次采集时机探讨

目的 探讨健康供者体内应用rhG-CSF初次采集造血于细胞以后二次外周血造血干细胞采集的时机.方法 38例二次采集外周血干细胞的健康供者皮下注射rhG-CSF 5 μg·kg-1·d-1,连用5 d,在第5、6天采集外周血移植物(A组);A组供者初次采集时的资料作为对照(B组);A组供者依据初次和二次采集的75%间隔时间分为C组(≤9个月,n=30)和D组(>9个月,n=8).应用流式细胞术检测各组供者外周血采集物中的淋巴细胞,CD3+、CD3+CD4+、CD3+CD8+、CD14+、CD34+细胞以及CD3+CD4-CD8-T细胞的数量.结果 A组供者外周血采集物中淋巴细胞CD3+CD8+(25.51×108)和CD34+细胞(0.51×108)的中位含量显著低于B组(31.55×108和0.70×108,P<0.05);C组供者CD3+CD8+(23.42×108)和CD34+细胞(0.42×108)的中位含量显著低于B组(P<0.05);D组供者淋巴细胞,CD3+、CD3+CD4+、CD3+CD8+、CD14+、CD34+细胞以及CD3+CD4-CD8-T细胞的中位含量与B组的差异无统计学意义(P>0.05).A、C和D三组采集物中CD4+与CD8+细胞的比值、单核细胞与CD3+细胞的比值以及CD3+CD4-CD8-T细胞与CD3+细胞的比值与B组的差异均无统计学意义(P>0.05).38名健康供者初次和二次采集的间隔时间与二次采集物中的CD34+细胞存在显著的相关性(r=0.357,P=0.028).结论 健康供者二次采集外周血造血干细胞的时机以初次采集的9个月后为宜,9个月内采集应适当增加循环血量以保证移植物中的免疫和造血组分能满足临床需要.     

何谓细胞毒性T淋巴细胞?

问:何谓细胞毒性T淋巴细胞? 答:一类直接杀伤胞内病原体感染靶细胞、肿瘤细胞、同种异体移植物的胸腺依赖性淋巴细胞(T淋巴细胞)亚群,又称杀伤性T淋巴细胞,简称CTL或Tc.Tc在识别和杀伤病毒感染靶细胞时,需要识别外来抗原和自身主要组织相容性复合体(MHC)Ⅰ类抗原结合形成的复合物,人Tc表型为CD8+、CD28+.白细胞介素-2(IL-2)等细胞因子对Tc的分化和效应功能有重要的调节作用.穿孔素(perforin)和淋巴毒素(LT,又称肿瘤坏死因子-β)是Tc杀伤靶细胞过程中释放的主要介质.     

特发性血小板减少性紫癜患者外周血T细胞的杀伤细胞免疫球蛋白样受体表达研究

杀伤细胞免疫球蛋白样受体(killer Ig-like receptors,KIR)是近年发现的细胞表面糖蛋白受体,除表达于NK细胞外还表达于部分T细胞,主要为CD8~+ 细胞毒性T淋巴细胞(cytotoxic lymphocyte,CTL)~[1].     

Generation of cytotoxic T lymphocytes specific for human cytomegalovirus using dendritic cells in vitro

For the adoptive immunotherapy in immunodeficient bone marrow transplant recipients to prevent and treat human cytomegalovirus (HCMV)-associated diseases, HCMV-pulsed dendritic cells (DCs) were used as antigen-presenting cells for the induction of cytotoxic T lymphocytes (CTLs) specific to HCMV antigens in vitro. The antiviral CTL responses induced by HCMV-pulsed DCs were as highly efficient as those induced by HCMV-infected dermal fibroblasts, and endogenous viral gene expression was not required to induce virus-specific T-cell lines. The strong cytotoxic activity against HCMV-pp65, known as HCMV major antigen, was identified using autologous B lymphoblastoid cell line expressing pp65 antigen. The cytotoxic activity toward HCMV-infected target cells was found to be mediated primarily by CD8+ T cells, although both CD8+ cells and CD4+ cells were able to lyse autologous virus-infected target cells. The CTLs contained a mixture of effector cells that recognized virus peptides in the context of major histocompatibility complex. This system may be useful for defining the cellular immune response to HCMV and for the treatment of HCMV infection in immunocompromised patients.     

The generation and characterization of LMP2-specific CTLs for use as adoptive transfer from patients with relapsed EBV-positive Hodgkin disease

Cellular adoptive immunotherapy for virus-associated malignant disease is an attractive strategy, since viral antigens provide targets for specific T lymphocytes. In Epstein-Barr virus (EBV)-positive Hodgkin disease (HD), a limited number of EBV-encoded antigens such as the latent membrane antigens (LMP) 1 and 2 are expressed on the malignant Reed-Sternberg cells. The authors aimed to generate cytotoxic T lymphocytes (CTLs) from patients with relapsed HD by specifically targeting LMP2A. Patients with relapsed HD have highly immunosuppressive tumors and have been heavily pretreated with cytotoxic agents. As a result, monocytes and lymphocytes are numerically reduced and functionally impaired. Approaches using dendritic cells (DCs) as the sole antigen-presenting cell to expand LMP2-specific CTL lines in vitro have proved impractical. The authors now show how small amounts of patient peripheral blood can be used to produce DCs expressing LMP2 after Ad5F35 transduction, and how an initial reactivation of LMP2-specific CTLs can be followed by stimulation with lymphoblastoid cell lines overexpressing LMP2 from the same vector. Large numbers of LMP2-specific cytotoxic lymphocytes are produced that contain both CD4+ and CD8+ T cells (favoring long-term persistence in vivo) and recognize multiple LMP2 epitopes (minimizing the risk of tumor antigen loss variants). This approach is being used in a current clinical trial.     

Expansion of melanoma-specific cytolytic CD8+ T cell precursors in patients with metastatic melanoma vaccinated with CD34+ progenitor-derived dendritic cells

Cancer vaccines aim at inducing (a) tumor-specific effector T cells able to reduce/eliminate the tumor mass, and (b) long-lasting tumor-specific memory T cells able to control tumor relapse. We have shown earlier, in 18 human histocompatibility leukocyte antigen (HLA)-A*0201 patients with metastatic melanoma, that vaccination with peptide-loaded CD34-dendritic cells (DCs) leads to expansion of melanoma-specific interferon gamma-producing CD8+ T cells in the blood. Here, we show in 9 out of 12 analyzed patients the expansion of cytolytic CD8+ T cell precursors specific for melanoma differentiation antigens. These precursors yield, upon single restimulation with melanoma peptide-pulsed DCs, cytotoxic T lymphocytes (CTLs) able to kill melanoma cells. Melanoma-specific CTLs can be grown in vitro and can be detected in three assays: (a) melanoma tetramer binding, (b) killing of melanoma peptide-pulsed T2 cells, and (c) killing of HLA-A*0201 melanoma cells. The cytolytic activity of expanded CTLs correlates with the frequency of melanoma tetramer binding CD8+ T cells. Thus, CD34-DC vaccines can expand melanoma-specific CTL precursors that can kill melanoma antigen-expressing targets. These results justify the design of larger follow-up studies to assess the immunological and clinical response to peptide-pulsed CD34-DC vaccines.     

A nonimmunogenic sarcoma transduced with the cDNA for interferon gamma elicits CD8+ T cells against the wild-type tumor: correlation with antigen presentation capability.

To be recognized by CD8+ T lymphocytes, target cells must process and present peptide antigens in the context of major histocompatibility complex (MHC) class I molecules. The nonimmunogenic, low class I-expressing, methylcholanthrene (MCA)-induced murine sarcoma cell line, MCA 101, is a poor presenter of endogenously generated viral antigens to specific CD8+ T lymphocytes and cannot be used to generate tumor infiltrating lymphocytes (TIL). Since interferon gamma (IFN-gamma) has been shown to upregulate three sets of molecules important for antigen processing and presentation, we retrovirally transduced wild-type MCA 101 (101.WT) tumor with the mIFN-gamma cDNA to create the 101.NAT cell line. Unlike 101.WT, some clones of retrovirally transduced 101.NAT tumor expressed high levels of class I, and could be used to generate CD8+ TIL. More importantly, these TIL were therapeutic in vivo against established pulmonary metastases from the wild-type tumor. Although not uniformly cytotoxic amongst several separate cultures, these TIL did specifically release cytokines (IFN-gamma and tumor necrosis factor-alpha) in response to 101.WT targets. 101.WT's antigen presentation deficit was also reversed by gene modification with mIFN-gamma cDNA. 101.NAT had a greatly improved capacity to present viral antigens to CD8+ cytotoxic T lymphocytes. These findings show that a nonimmunogenic tumor, incapable of generating a CD8+ T cell immune response, could be gene-modified to generate a therapeutically useful immune response against the wild-type tumor. This strategy may be useful in developing treatments for tumor histologies not thought to be susceptible to T cell-based immunotherapy.     

Cytotoxic T lymphocytes simultaneously targeting multiple tumor-associated antigens to treat EBV negative lymphoma

Although immunotherapy with Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) can treat EBV-associated Hodgkin and non-Hodgkin lymphoma (HL/NHL), more than 50% of such tumors are EBV negative. We now describe an approach that allows us to consistently generate, in a single line, CTLs that recognize a wide spectrum of nonviral tumor-associated antigens (TAAs) expressed by human HL/NHL, including Survivin, MAGE-A4, Synovial sarcoma X (SSX2), preferentially expressed antigen in melanoma (PRAME) and NY-ESO-1. We could generate these CTLs from nine of nine healthy donors and five of eight lymphoma patients, irrespective of human leukocyte antigen (HLA) type. We reactivated TAA-directed T cells ex vivo, by stimulation with dendritic cells (DCs) pulsed with overlapping peptide libraries spanning the chosen antigens in the presence of an optimized Th1-polarizing, prosurvival/proliferative and Treg inhibitory cytokine combination. The resultant lines of CD4(+) and CD8(+), polycytokine-producing T cells are directed against a multiplicity of epitopes expressed on the selected TAAs, with cytolytic activity against autologous tumor cells. Infusion of such multispecific monocultures may extend the benefits of CTL therapy to treatment even of EBV negative HL and NHL.     

Tetanus toxoid provides efficient T-cell help for the induction of HA-1(H) cytotoxic T cells

BACKGROUND: In vitro generation and expansion of leukemia‐reactive T cells may improve the efficacy and specificity of cellular immunotherapy against hematologic malignancies in the context of allogeneic stem cell transplantation. Since the expression of minor histocompatibility antigen HA‐1^H is limited to hematopoietic cells, ex vivo generated HA‐1^H‐specific CD8+ cytotoxic T lymphocytes (CTLs) can be used for adoptive immunotherapy. STUDY DESIGN AND METHODS: Numerous studies have shown that primary CTL induction from naïve precursors requires professional antigen‐presenting cells. Here, the feasibility of ex vivo induction of HA‐1^H‐specific CD8+ CTLs is demonstrated from unfractionated peripheral blood mononuclear cells (PBMNCs) from healthy blood donors when CD4+ T‐cell help is provided during primary stimulation. As a stimulus for the induction of T‐cell help, tetanus toxoid (TT) was used. RESULTS: After the second restimulation cycle, approximately 1 percent of CD8+ T cells stained positively with the HLA‐A*0201/HA‐1^H pentamer. Positive T cells were further expanded more than 1000‐fold by antigen‐independent stimulation with anti‐CD3/CD28 monoclonal antibodies. HA‐1^H‐induced T cells showed the classical phenotype for CD8+ memory effector cells: the phenotype changed from a mixed CD45RA/RO phenotype to an activated phenotype characterized by high expression of CD45RO and no expression of CCR7. The generated T cells revealed a very potent CTL response, even at low E:T ratios. CONCLUSION: This study demonstrates that TT provides a very potent and cost‐effective tool for the in vitro induction of antigen‐specific CTLs from precursor PBMNCs that can easily be adapted to GMP conditions for translational purposes.     

MHC class II-restricted tumor antigens recognized by CD4+ T cells: new strategies for cancer vaccine design

The adoptive transfer of tumor-infiltrating lymphocytes (TIL) can mediate tumor regression in patients with melanoma. This finding has led to the identification and characterization of tumor-associated antigens recognized by CD8+ TIL. Several clinical trials based on the genes recognized by these CD8+ T cells have been attempted, but with only limited success. Meanwhile, increasing evidence has demonstrated that CD4+ T cells play important roles in generating and maintaining antitumor immune responses in animal models. These data suggest that it may be necessary to engage both CD4+ and CD8+ T cells for more effective antitumor immunotherapy. In this report, we review emerging molecular approaches in cloning major histocompatibility complex (MHC) class II restricted tumor antigens recognized by CD4+ T cells as well as approaches to identify new MHC class II-restricted epitopes from known tumor antigens recognized by CD8+ cytotoxic T lymphocytes and/or antibodies. Progress made in this field has shed light on the roles of tumor antigen-specific CD4+ T cells in humans; it has also provided new insights into the understanding of tumor genesis and the interaction between tumor and the immune system. More importantly, the discovery of MHC class II-restricted tumor antigens has provided opportunities for developing a new generation of cancer vaccines aimed at eliciting both CD4+ and CD8+ T-cell responses against tumor.     

Bispecific single-chain diabody-mediated killing of endoglin-positive endothelial cells by cytotoxic T lymphocytes

We present a novel vascular tumor therapy approach based on lysing endothelial cells by cytotoxic T lymphocytes (CTLs). Retargeting of CTLs is achieved by a recombinant bispecific antibody molecule (bispecific single-chain diabody) directed against human endoglin (CD105, EDG) and the T-cell coreceptor CD3 (scDb EDGCD3). Bacterially expressed scDb EDGCD3 was able to bind to endoglin-expressing endothelial cells as well as CD3-expressing T lymphocytes. The single-chain diabody mediated killing of endothelial cells (HUVEC, HMEC) by activated cytotoxic T lymphocytes at picomolar concentrations, and cells not expressing endoglin were not affected. Because endoglin is up-regulated in the vasculature of many solid tumors, this antibody molecule should be capable of lysing tumor endothelial cells and thus destroying the vascular bed of the tumor.