A novel high-affinity human monoclonal antibody to mesothelin.

Abstract:

:Mesothelin is a glycosylphosphatidylinositol-anchored glycoprotein that is highly expressed on the cell surface of mesothelioma, ovarian cancer and other malignant tumors. The interaction between mesothelin and CA125 (also called MUC16) may facilitate the implantation and metastasis of tumors in the peritoneal cavity. A desirable therapeutic agent involves finding a fully human monoclonal antibody (mAb) that binds to mesothelin or CA125 and inhibits their interaction. Here, we report the identification of a novel human mAb to mesothelin. HN1, a human single-chain Fv specific for mesothelin, was isolated from a naïve human single-chain variable fragment (scFv) phage display library. To investigate HN1 as a potential therapeutic, we generated a fully human IgG with the γ 1 heavy chain and the κ light chain and an immuntoxin by fusing the HN1 scFv to a truncated Pseudomonas exotoxin A. The HN1 IgG kills cancer cells with very strong antibody-dependent cell-mediated cytotoxicity. HN1 binds a conformation-sensitive epitope in human mesothelin with high affinity (K(D) = 3 nM). The HN1 epitope is different from that of SS1, a mouse Fv used to develop therapeutic antibodies that are currently in clinical trials. HN1 binds to cell surface-associated mesothelin on human mesothelioma, ovarian cancer, lung adenocarcinoma and pancreatic cancer cells. In addition, HN1 can functionally block the interaction of mesothelin and CA125 on cancer cells. Most importantly, because the HN1 immuntoxin kills mesothelin-expressing cancer cells with high cytotoxic activity, we believe that it has significant potential for mesothelin-expressing cancer treatment and diagnosis.

journal_name

Int J Cancer

authors

Ho M,Feng M,Fisher RJ,Rader C,Pastan I

doi

10.1002/ijc.25557

subject

Has Abstract

pub_date

2011-05-01 00:00:00

pages

2020-30

issue

9

eissn

0020-7136

issn

1097-0215

journal_volume

128

pub_type

杂志文章
  • Intraepithelial p63-dependent expression of distinct components of cell adhesion complexes in normal esophageal mucosa and squamous cell carcinoma.

    abstract::TP63 gene is a member of TP53 tumor suppressor gene family that encodes several protein isoforms involved in the process of epithelial stratification and in epithelial-mesenchyme interactions. TP63 is amplified in a significant proportion of squamous cell carcinoma of the esophagus (ESCC), resulting in the hyper-expre...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.25221

    authors: Thépot A,Hautefeuille A,Cros MP,Abedi-Ardekani B,Pétré A,Damour O,Krutovskikh V,Hainaut P

    更新日期:2010-11-01 00:00:00

  • Food-frequency questionnaire-based estimates of total antioxidant capacity and risk of non-Hodgkin lymphoma.

    abstract::Antioxidants, primarily from fruits and vegetables, have been hypothesized to protect against non-Hodgkin lymphoma (NHL). The oxygen radical absorbance capacity (ORAC) assay, which measures total antioxidant capacity of individual foods and accounts for synergism, can be estimated using a food-frequency questionnaire ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.26491

    authors: Holtan SG,O'Connor HM,Fredericksen ZS,Liebow M,Thompson CA,Macon WR,Micallef IN,Wang AH,Slager SL,Habermann TM,Call TG,Cerhan JR

    更新日期:2012-09-01 00:00:00

  • Immortalization of oral keratinocytes by functional inactivation of the p53 and pRb pathways.

    abstract::A subgroup of head and neck squamous cell carcinomas (HNSCCs) contains high-risk human papillomavirus-type 16 (HPV16). The viral E6 and E7 oncoproteins inactivate the p53 and pRb proteins, respectively. We examined the causative effect of HPV16 E6 and E7 expression on the immortalization of normal oral keratinocytes (...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.25474

    authors: Smeets SJ,van der Plas M,Schaaij-Visser TB,van Veen EA,van Meerloo J,Braakhuis BJ,Steenbergen RD,Brakenhoff RH

    更新日期:2011-04-01 00:00:00

  • Somatic mutations of the lysyl oxidase gene on chromosome 5q23.1 in colorectal tumors.

    abstract::Lysyl oxidase (LOX), a copper-dependent amine oxidase, has been implicated in tumor suppression and cell growth regulation. The chromosomal locus of LOX, 5q23, is affected by loss of heterozygosity (LOH) in colon cancer, suggesting that the LOX gene could be affected by LOH and consequently, loss or reduction of LOX f...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.10035

    authors: Csiszar K,Fong SF,Ujfalusi A,Krawetz SA,Salvati EP,Mackenzie JW,Boyd CD

    更新日期:2002-02-10 00:00:00

  • Expression of the c-Ha-ras and neu oncogenes in DMBA-induced, anti-estrogen-treated rat mammary tumors.

    abstract::Dimethylbenzanthracene (DMBA)-induced rat mammary tumors were analyzed for the structure and expression of the oncogenes c-Ha-ras and neu and the effects of anti-estrogen treatment. Tumor samples were divided into 3 groups, the first consisting of untreated tumors, the second of anti-estrogen (toremifene)-treated unre...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910420524

    authors: Vuorio T,Wärri A,Sandberg M,Alitalo K,Vuorio E

    更新日期:1988-11-15 00:00:00

  • Heterogeneous expression of melanoma-associated antigens and HLA-A2 in metastatic melanoma in vivo.

    abstract::MART-1/MelanA and Pmel17/gp100 are melanoma-associated antigens (MAAs) that can be recognized by tumor-infiltrating lymphocytes (TILs) capable of mediating successful adoptive therapy in vivo. Analysis of melanoma cell lines in vitro has demonstrated that heterogeneous antigen expression in the context of class I MHC ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19980209)75:4<517::aid-ijc

    authors: Cormier JN,Hijazi YM,Abati A,Fetsch P,Bettinotti M,Steinberg SM,Rosenberg SA,Marincola FM

    更新日期:1998-02-09 00:00:00

  • Telomerase reverse transcriptase mutations are independent predictor of disease-free survival in Middle Eastern papillary thyroid cancer.

    abstract::Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Tumor recurrence occurs in ∼20% of PTCs and some reach advanced stages. Promoter mutation in the telomerase reverse transcriptase (TERT) gene is identified to be a prognostic marker in PTC. However, the contribution of TERT promoter mutation ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.31225

    authors: Bu R,Siraj AK,Divya SP,Kong Y,Parvathareddy SK,Al-Rasheed M,Al-Obaisi KAS,Victoria IG,Al-Sobhi SS,Al-Dawish M,Al-Dayel F,Al-Kuraya KS

    更新日期:2018-05-15 00:00:00

  • Family history of cancer and stomach cancer risk.

    abstract::A family history of stomach cancer in first-degree relatives increases the risk of stomach cancer, but uncertainties remain as concerns the variation of the risk according to age, sex and type of relative, as well as on the role of family history of other cancers. We investigated the issue using data from a multicentr...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.23688

    authors: Foschi R,Lucenteforte E,Bosetti C,Bertuccio P,Tavani A,La Vecchia C,Negri E

    更新日期:2008-09-15 00:00:00

  • Prognosis and chemosensitivity of deficient MMR phenotype in patients with metastatic colorectal cancer: An AGEO retrospective multicenter study.

    abstract::Mismatch repair-deficient (dMMR) and/or microsatellite instability-high (MSI) colorectal cancers (CRC) represent about 5% of metastatic CRC (mCRC). Prognosis and chemosensitivity of dMMR/MSI mCRC remain unclear. This multicenter study included consecutive patients with dMMR/MSI mCRC from 2007 to 2017. The primary endp...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.32879

    authors: Tougeron D,Sueur B,Zaanan A,de la Fouchardiére C,Sefrioui D,Lecomte T,Aparicio T,Des Guetz G,Artru P,Hautefeuille V,Coriat R,Moulin V,Locher C,Touchefeu Y,Lecaille C,Goujon G,Ferru A,Evrard C,Chautard R,Gentilhomme

    更新日期:2020-07-01 00:00:00

  • Incidence rates of leukemias, lymphomas and myelomas in Italy: geographic distribution and NHL histotypes.

    abstract::The annual incidence of non-Hodgkin's lymphomas is increasing by 3 to 4% in different parts of the developed world, while rates for Hodgkin's disease, myelomas and leukemias are more stable. In the case of this group of malignancies, hypothesis generation on risk factors has been limited by the use of the ICD classifi...

    journal_title:International journal of cancer

    pub_type: 杂志文章,多中心研究

    doi:10.1002/(SICI)1097-0215(19961009)68:2<156::AID-IJC

    authors: Masala G,Di Lollo S,Picoco C,Crosignani P,Demicheli V,Fontana A,Funtó I,Miligi L,Nanni O,Papucci A,Ramazzotti V,Rodella S,Stagnaro E,Tumino R,Viganó C,Vindigni C,Seniori Costantini A,Vineis P

    更新日期:1996-10-09 00:00:00

  • Recovery of leukocyte function after super-high-dose chemotherapy with peripheral blood stem cell transplantation in testicular cancer patients.

    abstract::Leukocyte functions (superoxide production and phagocytosis) were evaluated in patients with testicular cancer who had undergone super-high-dose chemotherapy (SHDT) with peripheral blood stem cell transplantation (PBSCT). In 5 patients with advanced or relapsed testicular cancer who received 8 cycles of SHDT with PBSC...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19970703)72:1<39::aid-ijc5

    authors: Yamada Y,Hara I,Gohji K,Okada H,Arakawa S,Kamidono S

    更新日期:1997-07-03 00:00:00

  • Correlation between the metastasizing activity of in vitro spontaneously transformed hamster cells and their natural resistance-depressing activity.

    abstract::In our previous experiments in Syrian hamsters the in vivo semiquantitative method of determination of the natural resistance-depressing (NRD) activity of tumor cells was described. It was demonstrated that inactivated cells of different tissue culture cell lines derived from in vivo tumors in contrast to normal, or i...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910300315

    authors: Deichman GI,Kluchareva TE,Kashkina LM,Matveeva VA,Vendrov EL,Zemtsova VI

    更新日期:1982-09-15 00:00:00

  • Lymphotoxin: an anticarcinogenic lymphokine as measured by inhibition of chemical carcinogen or ultraviolet-irradiation-induced transformation of Syrian hamster cells.

    abstract::Syrian-hamster-derived lymphotoxin inhibits benzo(a)pyrene and ultraviolet carcinogen-induced in vitro morphologic transformation of diploid secondary passage hamster embryo cells. When lymphotoxin is added up to 4 days post carcinogen, the reduction in the frequency of morphologic transformation 6 days after carcinog...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910270108

    authors: Evans CH,DiPaolo JA

    更新日期:1981-01-15 00:00:00

  • Antibodies reactive with the mouse mammary tumor virus in sera of breast cancer patients.

    abstract::IgG binding to purified mouse mammary tumor virus (MuMTV) was quantitated by an enzyme-linked immunoassay (ELISA) using sera from patients with breast cancer or benign breast disease, or from healthy age-matched controls. Significantly greater binding (p<0.01) was found in breast-cancer-derived sera than in the other ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910250606

    authors: Witkin SS,Sarkar NH,Kinne DW,Good RA,Day NK

    更新日期:1980-06-15 00:00:00

  • Simultaneous presence of EBNA-positive and colony-forming cells in peripheral blood of patients with infectious mononucleosis.

    abstract::EBNA-positive lymphoblast cells were detected in 0.1 to 0.9% of the T-cell-depleted lymphocytes obtained from peripheral blood samples of five patients with infectious mononucleosis (IM). The same blood specimens from four of the five patients contained cells that formed EBNA-positive colonies in soft agar containing ...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910230603

    authors: Katsuki T,Hinuma Y,Saito T,Yamamoto J,Hirashima Y,Sudoh H,Deguchi M,Motokawa M

    更新日期:1979-06-15 00:00:00

  • Different pattern of loss of heterozygosity among endocervical-type adenocarcinoma, endometrioid-type adenocarcinoma and adenoma malignum of the uterine cervix.

    abstract::It is unclear which chromosome arms frequently show loss of heterozygosity (LOH) in adenocarcinoma of the uterine cervix. To identify such chromosomal arms, LOH on 52 different chromosome loci was examined using laser capture microdissection and PCR-LOH analysis in 25 common-type adenocarcinomas, comprising 13 cases o...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.10228

    authors: Tsuda H,Takarabe T,Okada S,Uchida H,Kasamatsu T,Yamada T,Tsunematsu R,Ohmi K,Hirohashi S

    更新日期:2002-04-10 00:00:00

  • Human papillomavirus-related anogenital premalignancies and cancer in renal transplant recipients: A Danish nationwide, registry-based cohort study.

    abstract::In this registry-based cohort study, we estimated the risk of human papillomavirus (HPV)-related anogenital premalignancies and cancer in renal transplant recipients (RTRs) compared to a nontransplanted comparison cohort. We identified all first-time RTRs in Denmark during 1990-2015 in a nationwide nephrology register...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.32565

    authors: Reinholdt K,Thomsen LT,Dehlendorff C,Larsen HK,Sørensen SS,Haedersdal M,Kjaer SK

    更新日期:2020-05-01 00:00:00

  • Suppression of malignant growth of human breast cancer cells by ectopic expression of integrin-linked kinase.

    abstract::Allelic loss at the short arm of chromosome 11 is one of the most common and potent events in the progression and metastasis of breast cancer. Here, we present evidence that the Integrin-Linked Kinase (ILK) gene maps to the commonly deleted chromosome 11p15.5 and suppresses malignant growth of human breast cancer cell...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.20340

    authors: Chen P,Shen WZ,Karnik P

    更新日期:2004-10-10 00:00:00

  • Comparative expression of the psoriasin (S100A7) and S100C genes in breast carcinoma and co-localization to human chromosome 1q21-q22.

    abstract::Using differential screening of a breast cancer cDNA library, we isolated a cDNA encoding the psoriasin (S100A7) protein, previously identified in psoriatic epidermis. In the present study, we demonstrate that the psoriasin gene is expressed in breast cancer cell lines and in cancer cells of some breast carcinomas but...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910630225

    authors: Moog-Lutz C,Bouillet P,Régnier CH,Tomasetto C,Mattei MG,Chenard MP,Anglard P,Rio MC,Basset P

    更新日期:1995-10-09 00:00:00

  • Association between breast cancer risk and disease aggressiveness: Characterizing underlying gene expression patterns.

    abstract::The association between breast cancer risk defined by the Tyrer-Cuzick score (TC) and disease prognosis is not well established. Here, we investigated the relationship between 5-year TC and disease aggressiveness and then characterized underlying molecular processes. In a case-only study (n = 2474), we studied the ass...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.33270

    authors: Ugalde-Morales E,Grassmann F,Humphreys K,Li J,Eriksson M,Tobin NP,Borg Å,Vallon-Christersson J,Hall P,Czene K

    更新日期:2021-02-15 00:00:00

  • Role of folate receptor and reduced folate carrier in the transport of 5-methyltetrahydrofolic acid in human ovarian carcinoma cells.

    abstract::Folate receptor-alpha (FR-alpha) is generally over-expressed in non-mucinous human ovarian carcinomas. The meaning of FR-alpha over-expression and its role in the 5-methyltetrahydrofolic acid (N5-CH3-H4PteGlu) transport in such tumors is not clear, especially compared with the reduced folate carrier (RFC), the other k...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0215(19980105)75:1<125::aid-ijc

    authors: Corona G,Giannini F,Fabris M,Toffoli G,Boiocchi M

    更新日期:1998-01-05 00:00:00

  • Serological survey and virus isolation of simian T-cell leukemia/T-lymphotropic virus type I (STLV-I) in non-human primates in their native countries.

    abstract::Infection with a simian retrovirus (STLV-I) closely related to human T-lymphotropic virus type I (HTLV-I) was investigated in non-human primates living in their native countries in Africa and Asia. Serum antibodies cross-reacting with HTLV-I antigens were detected in 85 of 567 non-human primates of 30 species. Seropos...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910400219

    authors: Ishikawa K,Fukasawa M,Tsujimoto H,Else JG,Isahakia M,Ubhi NK,Ishida T,Takenaka O,Kawamoto Y,Shotake T

    更新日期:1987-08-15 00:00:00

  • Inhibition of syngeneic fibrosarcoma growth by lymphocytes sensitized on tumor-cell monolayers in the presence of the thymic humoral factor.

    abstract::The present experiments were performed to investigate the possibility of inhibiting tumor growth in vivo with syngeneic lymphocytes sensitized in vitro on monolayers of the tumor under test, and to study the effect of a thymic humoral factor (THF) in this sensitization process. Monolayers of fibrosarcoma cells were us...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910150612

    authors: Small M,Trainin N

    更新日期:1975-06-15 00:00:00

  • Mutation and expression of the p53 gene in malignant melanoma cell lines.

    abstract::Three monoclonal antibodies (MAbs) against p53 protein (PAb 24o, DO-I and PAb1801) were used to define the immunophenotype of 13 melanoma cell lines. Immunoreactions could be detected in 12 out of 13 cell lines by using the indirect immunofluorescence technique. In 7 of these the majority of cells displayed cytoplasmi...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910540427

    authors: Weiss J,Schwechheimer K,Cavenee WK,Herlyn M,Arden KC

    更新日期:1993-06-19 00:00:00

  • Dissecting the journey to breast cancer diagnosis in sub-Saharan Africa: Findings from the multicountry ABC-DO cohort study.

    abstract::Most breast cancer patients in sub-Saharan Africa are diagnosed at advanced stages after prolonged symptomatic periods. In the multicountry African Breast Cancer-Disparities in Outcomes cohort, we dissected the diagnostic journey to inform downstaging interventions. At hospital presentation for breast cancer, women re...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.33209

    authors: Foerster M,McKenzie F,Zietsman A,Galukande M,Anele A,Adisa C,Parham G,Pinder L,Schüz J,McCormack V,Dos-Santos-Silva I

    更新日期:2021-01-15 00:00:00

  • Circulating adipokine concentrations and risk of five obesity-related cancers: A Mendelian randomization study.

    abstract::Obesity is considered a chronic inflammatory state characterized by continued secretion of adipokines and cytokines. Experimental and epidemiological evidence indicates that circulating adipokines may be associated with the development of obesity-related cancers, but it is unclear if these associations are causal or c...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.33338

    authors: Dimou NL,Papadimitriou N,Mariosa D,Johansson M,Brennan P,Peters U,Chanock SJ,Purdue M,Bishop DT,Gago-Dominquez M,Giles GG,Moreno V,Platz EA,Tangen CM,Wolk A,Zheng W,Wu X,Campbell PT,Giovannucci E,Lin Y,CCFR, Endom

    更新日期:2020-10-10 00:00:00

  • The presence of concanavalin-A(Con-A)-like molecules on natural-killer (NK)-sensitive target cells: their possible role in swainsonine-augmented human NK cytotoxicity.

    abstract::In the present study we examined the expression of concanavalin-A(Con-A)-like molecules on natural-killer (NK)-sensitive target cells and investigated their possible role in the human NK-cell phenomenon. The incubation of either peripheral-blood lymphocytes (PBL) or large granular lymphocytes (LGL) with swainsonine (S...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910520428

    authors: Yagita M,Noda I,Maehara M,Fujieda S,Inoue Y,Hoshino T,Saksela E

    更新日期:1992-10-21 00:00:00

  • DT-diaphorase as a determinant of sensitivity to adriamycin in non-small-cell lung-cancer cell lines.

    abstract::We have reported the establishment of a mitomycin-C (MMC)-resistant non-small-cell lung-cancer cell line, PC-9/MC4. As determined by an MTT assay, this resistant cell line was found to be 4 times more sensitive to adriamycin (ADM) than was the parental PC-9. There were no significant differences in sensitivity to etop...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.2910590211

    authors: Kasahara K,Shibata K,Bando T,Numata Y,Fujimura M,Matsuda T

    更新日期:1994-10-15 00:00:00

  • Association of HPV35 with cervical carcinogenesis among women of African ancestry: Evidence of viral-host interaction with implications for disease intervention.

    abstract::HPV35 has been found in only ∼2% of invasive cervical cancers (ICC) worldwide but up to 10% in Sub-Saharan Africa, warranting further investigation and consideration of impact on preventive strategies. We studied HPV35 and ethnicity, in relation to the known steps in cervical carcinogenesis, using multiple large epide...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.33033

    authors: Pinheiro M,Gage JC,Clifford GM,Demarco M,Cheung LC,Chen Z,Yeager M,Cullen M,Boland JF,Chen X,Raine-Bennett T,Steinberg M,Bass S,Befano B,Xiao Y,Tenet V,Walker J,Zuna R,Poitras NE,Gold MA,Dunn T,Yu K,Zhu B,Bu

    更新日期:2020-11-15 00:00:00

  • Serum endostatin levels correlate with enhanced extracellular matrix degradation and poor patients' prognosis in bladder cancer.

    abstract::Endostatin, the proteolytic fragment of collagen XVIII, is an inhibitor of angiogenesis and tumor growth. Interestingly, elevated circulating endostatin levels have been found to correlate with poor patients' prognosis in several cancers. The aim of this study was to assess the prognostic value of endostatin in bladde...

    journal_title:International journal of cancer

    pub_type: 杂志文章

    doi:10.1002/ijc.26343

    authors: Szarvas T,László V,Vom Dorp F,Reis H,Szendröi A,Romics I,Tilki D,Rübben H,Ergün S

    更新日期:2012-06-15 00:00:00