Research Topics
Genomes and Genes
| Ira PastanSummaryAffiliation: National Institutes of Health Country: USA Publications
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Publications
Mesothelin, Stereocilin, and Otoancorin are predicted to have superhelical structures with ARM-type repeatsBangalore K Sathyanarayana
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 4264, USA
BMC Struct Biol 9:1. 2009..Mesothelin has been reported to be homologous to the deafness-related inner ear proteins otoancorin and stereocilin, for neither of which the three-dimensional structure is known...
Immunotoxin therapy of cancerIra Pastan
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institues of Health, 37 Convent Drive, Bethesda, MD 20892 4264, USA
Nat Rev Cancer 6:559-65. 2006..Results from clinical trials indicate that recombinant immunotoxins and similar agents that are designed to combine antibody selectivity with toxin cell-killing potency will be useful additions to cancer therapy...
An NIH career: from bedside to basic research and backIra Pastan
Laboratory of Molecular Biology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892-4264, USA
J Biol Chem 280:18553-7. 2005
Immunotoxin treatment of cancerIra Pastan
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Annu Rev Med 58:221-37. 2007..Strategies to overcome these limitations are being pursued...
New gene expressed in prostate: a potential target for T cell-mediated prostate cancer immunotherapyVittore Cereda
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA
Cancer Immunol Immunother 59:63-71. 2010..These studies thus identify NGEP as a potential target for T cell-mediated immunotherapy of prostate cancer...
Immunoglobulin superfamily receptor translocation associated 2 protein on lymphoma cell lines and hairy cell leukemia cells detected by novel monoclonal antibodiesTomoko Ise
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 4264, USA
Clin Cancer Res 11:87-96. 2005..To study the expression of the IRTA2 gene product, we produced monoclonal antibodies (MAbs) specific to IRTA2...
Five POTE paralogs and their splice variants are expressed in human prostate and encode proteins of different lengthsTapan K Bera
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 37, MSC 4264, 37 Convent Drive Room 5106, Bethesda, MD 20892 4264, USA
Gene 337:45-53. 2004..We also detect a noncoding transcript expressed on the opposite strand from POTE on chromosome 14 or 22. We speculate that POTE has an important signaling function in the reproductive system...
Characterization of the B cell epitopes associated with a truncated form of Pseudomonas exotoxin (PE38) used to make immunotoxins for the treatment of cancer patientsMasanori Onda
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892, USA
J Immunol 177:8822-34. 2006..Our results indicate that a relatively small number of discrete immunogenic sites are associated with PE38, most of which can be eliminated by point mutations...
A recombinant immunotoxin targeting CD22 with low immunogenicity, low nonspecific toxicity, and high antitumor activity in miceJohanna K Hansen
Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
J Immunother 33:297-304. 2010..Future studies will determine if these properties carry over to humans with cancer...
An immunotoxin with greatly reduced immunogenicity by identification and removal of B cell epitopesMasanori Onda
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4264, USA
Proc Natl Acad Sci U S A 105:11311-6. 2008..Elimination of B-cell epitopes is a promising approach to the production of less immunogenic proteins for therapeutic purposes...
Pretargeted radioimmunotherapy of mesothelin-expressing cancer using a tetravalent single-chain Fv-streptavidin fusion proteinNoriko Sato
Nuclear Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA
J Nucl Med 46:1201-9. 2005..The specific activity of DOTA-biotin had a significant effect on its tumor uptake. Therapeutic tumor doses were obtained without dose-limiting toxicity...
HA22 (R490A) is a recombinant immunotoxin with increased antitumor activity without an increase in animal toxicitySookhee Bang
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, 37 Convent Drive, Bethesda, MD 20892, USA
Clin Cancer Res 11:1545-50. 2005..Because HA22 (R490A) has increased antitumor activity without increased animal toxicity, immunotoxins with this mutation are candidates for clinical development...
PAGE4 is a cytoplasmic protein that is expressed in normal prostate and in prostate cancersCarlo Iavarone
Laboratory of Molecular Biology, Clinical Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
Mol Cancer Ther 1:329-35. 2002..Furthermore, cDNA microarray analysis indicates that the expression of lipoprotein lipase, a gene frequently deleted in prostate cancer, is down-regulated in a cell line that expresses PAGE4...
Megakaryocyte potentiation factor cleaved from mesothelin precursor is a useful tumor marker in the serum of patients with mesotheliomaMasanori Onda
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 4264, USA
Clin Cancer Res 12:4225-31. 2006..To establish monoclonal antibodies (mAb) against megakaryocyte potentiation factor (MPF) and detect MPF in the blood of patients with mesothelioma...
Selective POTE paralogs on chromosome 2 are expressed in human embryonic stem cellsTapan K Bera
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Stem Cells Dev 17:325-32. 2008..There is no detectable POTE gene expression in fetal tissues (ages 16-36 weeks). The POTE paralogs that are expressed in ES cells may have a specific function during lineage-specific differentiation of ES cells...
NGEP, a gene encoding a membrane protein detected only in prostate cancer and normal prostateTapan K Bera
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 101:3059-64. 2004..Because of its selective expression in prostate cancer and its presence on the cell surface, NGEP-L is a promising target for the antibody-based therapies of prostate cancer...
Pretargeted alpha emitting radioimmunotherapy using (213)Bi 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid-biotinZhengsheng Yao
Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, NIH, Bethesda, Maryland 20892, USA
Clin Cancer Res 10:3137-46. 2004..CONCLUSIONS: (213)Bi-DOTA-biotin, directed by the Pretarget method to tumor-targeted B3-SA, showed a therapeutic effect, although the therapeutic index was low. The source of the toxicity was most likely related to the renal toxicity...
The T cell receptor gamma chain alternate reading frame protein (TARP), a prostate-specific protein localized in mitochondriaHiroshi Maeda
Laboratory of Molecular Biology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892 4264, USA
J Biol Chem 279:24561-8. 2004..These data demonstrate that TARP is the first prostate-specific protein localizing in mitochondria and indicate that TARP, an androgen-regulated protein, may act on mitochondria to carry out its biological functions...
Anti-CD22 immunotoxin RFB4(dsFv)-PE38 (BL22) for CD22-positive hematologic malignancies of childhood: preclinical studies and phase I clinical trialAlan S Wayne
Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 1104, USA
Clin Cancer Res 16:1894-903. 2010..We conducted the first preclinical and phase I clinical studies of BL22 in that setting...
New monoclonal antibodies to mesothelin useful for immunohistochemistry, fluorescence-activated cell sorting, Western blotting, and ELISAMasanori Onda
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-4264, USA
Clin Cancer Res 11:5840-6. 2005....
A protease-resistant immunotoxin against CD22 with greatly increased activity against CLL and diminished animal toxicityJohn E Weldon
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892 4264, USA
Blood 113:3792-800. 2009..We conclude that HA22-LR advances the therapeutic efficacy of HA22 by using an approach that may be applicable to other PE-based immunotoxins...
Evolution and expression of chimeric POTE-actin genes in the human genomeYoomi Lee
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4264, USA
Proc Natl Acad Sci U S A 103:17885-90. 2006..These data demonstrate that insertion of a retroposon produced an altered functional POTE gene. This example indicates that new functional human genes can evolve by insertion of retroposons...
FCRL1 on chronic lymphocytic leukemia, hairy cell leukemia, and B-cell non-Hodgkin lymphoma as a target of immunotoxinsXing Du
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4264, USA
Blood 111:338-43. 2008..Our results suggest that anti-FCRL1 immunotoxin E9(Fv)-PE38 exhibits remarkably specific cytotoxicity and merits further evaluation for the treatment of FCRL1-positive malignancies, including CLL, HCL, FL, MCL, and other B-NHL...
Identification of cytotoxic T-lymphocyte epitope(s) and its agonist epitope(s) of a novel target for vaccine therapy (PAGE4)Junko Yokokawa
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD
Int J Cancer 121:595-605. 2007..The studies reported here are the first to describe a PAGE4 CTL epitope and its agonist epitope, and thus identify PAGE4 as a potentially useful target for vaccine-mediated therapy of prostate cancer...
A novel high-affinity human monoclonal antibody to mesothelinMitchell Ho
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4264, USA
Int J Cancer 128:2020-30. 2011..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...
The improvement of an anti-CD22 immunotoxin: conversion to single-chain and disulfide stabilized form and affinity maturation by alanine scanSeiji Kawa
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
MAbs 3:479-86. 2011..47 ± 0.090 ng/ml, IC 50(N34A): 0.048 ± 0.018 ng/ml)-fold compared to WT immunotoxin. The present study suggests that the N34A mutant of scdsFv-HA22-LR could have important consequences in a clinical setting...
Synergistic antitumor activity of taxol and immunotoxin SS1P in tumor-bearing miceYujian Zhang
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892-4264, USA
Clin Cancer Res 12:4695-701. 2006..This effect is not secondary to increased tumor uptake of the immunotoxin. Synergy could be due to improved immunotoxin distribution within the tumor or could involve factors released by other cell types in the tumors...
Palmitoylation of POTE family proteins for plasma membrane targetingSudipto Das
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 4264, USA
Biochem Biophys Res Commun 363:751-6. 2007..Multiple palmitoylation in the small CRRs can result in the strong association of whole POTEs with plasma membrane...
Topology of NGEP, a prostate-specific cell:cell junction protein widely expressed in many cancers of different grade levelSudipto Das
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 4264, USA
Cancer Res 68:6306-12. 2008..Our findings on the expression and the orientation of the NGEP protein serve as an important framework for the development of mAb targeting the extracellular regions of NGEP that could be used for prostate cancer immunotherapy...
Recombinant immunotoxin against B-cell malignancies with no immunogenicity in mice by removal of B-cell epitopesMasanori Onda
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4264, USA
Proc Natl Acad Sci U S A 108:5742-7. 2011..HA22-LR-8M also has greatly reduced antigenicity when exposed to sera from patients who have produced antibodies to HA22. The properties of HA22-LR-8M make it an excellent candidate for further clinical development...
A flow cytometry method to quantitate internalized immunotoxins shows that taxol synergistically increases cellular immunotoxins uptakeYujian Zhang
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 4264, USA
Cancer Res 70:1082-9. 2010..Further, we suggest one basis to understand why chemotherapy and antibody-based therapies cooperate when combined in cancer treatment...
Mesothelin expression in human lung cancerMitchell Ho
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA
Clin Cancer Res 13:1571-5. 2007..To investigate mesothelin as a new target for immunotherapy in lung cancer...
POTE paralogs are induced and differentially expressed in many cancersTapan K Bera
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-4264, USA
Cancer Res 66:52-6. 2006..It is likely that POTE has a unique role in primate biology...
Phase II trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with hairy cell leukemiaRobert J Kreitman
Laboratory of Molecular Biology, Laboratory of Clinical Pathology, and Medicine Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA
J Clin Oncol 27:2983-90. 2009..To conduct a phase II trial in chemoresistant hairy cell leukemia (HCL) with BL22, a recombinant anti-CD22 immunotoxin which showed phase I activity in HCL...
Expression of POTE protein in human testis detected by novel monoclonal antibodiesTomoko Ise
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4264, USA
Biochem Biophys Res Commun 365:603-8. 2008..By immunohistochemistry we demonstrated that the POTE protein is expressed in primary spermatocytes, implying a role in spermatogenesis...
Detection and quantitation of serum mesothelin, a tumor marker for patients with mesothelioma and ovarian cancerRaffit Hassan
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute NIH, 37 Convent Drive, Bethesda, MD 20892, USA
Clin Cancer Res 12:447-53. 2006..To determine whether mesothelin, a cell surface protein highly expressed in mesothelioma and ovarian cancer, is shed into serum and if so to accurately measure it...
Immunotoxins in the treatment of refractory hairy cell leukemiaRobert J Kreitman
Clinical Immunotherapy Section, Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 37, Room 5124b, Bethesda, MD 20892 4255, USA
Hematol Oncol Clin North Am 20:1137-51, viii. 2006..Both agents, termed LMB-2 and BL22, respectively, have been tested in patients who have HCL after failure of purine analogs and other therapies; major responses have been achieved in most patients...
Phase I trial of continuous infusion anti-mesothelin recombinant immunotoxin SS1PRobert J Kreitman
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 4264, USA
Clin Cancer Res 15:5274-9. 2009..To conduct a phase I trial of recombinant immunotoxin SS1P given by continuous infusion in chemoresistant solid tumors expressing mesothelin...
Discovery of the breast cancer gene BASE using a molecular approach to enrich for genes encoding membrane and secreted proteinsKristi A Egland
Laboratory of Molecular Biology and Cancer Genomics Office, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 100:1099-104. 2003..Further analysis of this library should yield additional gene products of use in the diagnosis or treatment of breast or prostate cancer...
Minimal residual disease in hairy cell leukemia patients assessed by clone-specific polymerase chain reactionEvgeny Arons
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA
Clin Cancer Res 12:2804-11. 2006..Thus, patient-specific RQ-PCR is the most sensitive test for MRD in HCL patients and could be used to determine maximal response in patients obtaining multiple cycles of nonmyelotoxic biological treatment for this disease...
Sandwich ELISAs for soluble immunoglobulin superfamily receptor translocation-associated 2 (IRTA2)/FcRH5 (CD307) proteins in human seraTomoko Ise
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892, USA
Clin Chem Lab Med 44:594-602. 2006..The membrane form is highly expressed on the surface of hairy cell leukemia (HCL) cells from patients. This study aimed to develop immunoassays for soluble IRTA2/FcRH5 proteins in human serum...
Killing of resistant cancer cells with low Bak by a combination of an antimesothelin immunotoxin and a TRAIL Receptor 2 agonist antibodyXing Du
Laboratory of Molecular Biology, Center for Cancer Research, and Pediatric Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland, USA
Clin Cancer Res 17:5926-34. 2011..Pancreatic cancers express mesothelin and are known to be resistant to most chemotherapeutic agents. The goal of this study is to treat pancreatic cancer with RIT by targeting mesothelin...
Humoral immune response to mesothelin in mesothelioma and ovarian cancer patientsMitchell Ho
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA
Clin Cancer Res 11:3814-20. 2005..Here we addressed the issue of whether mesothelin elicits a humoral immune response in patients with mesothelioma and ovarian cancer...
Novel anti-CD30 recombinant immunotoxins containing disulfide-stabilized Fv fragmentsSatoshi Nagata
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-4264, USA
Clin Cancer Res 8:2345-55. 2002..Two of these showed good cytotoxic activity to various CD30-positive cell lines. These newly produced immunotoxins should be additionally evaluated for the treatment of CD30-positive lymphomas...
Pulsed high-intensity focused ultrasound enhances uptake of radiolabeled monoclonal antibody to human epidermoid tumor in nude miceAlfia Khaibullina
Department of Radiology, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA
J Nucl Med 49:295-302. 2008..The aim of this study was to determine if pulsed high-intensity focused ultrasound (HIFU) exposures could enhance tumor uptake of (111)In-MX-B3, a murine IgG1kappa monoclonal antibody directed against the Le(y) antigen...
NGEP, a prostate-specific plasma membrane protein that promotes the association of LNCaP cellsSudipto Das
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute NIH, 37 Convent Drive, Bethesda, MD 20892, USA
Cancer Res 67:1594-601. 2007..Our results suggest that NGEP-L has a role in promoting cell contact-dependent interactions of LNCaP prostate cancer cells and also that NGEP is a promising immunotherapy target for prostate cancer...
Releasable PEGylation of mesothelin targeted immunotoxin SS1P achieves single dosage complete regression of a human carcinoma in miceDavid Filpula
Enzon Pharmaceuticals, Incorporated, 20 Kingsbridge Road, Piscataway, New Jersey 08854, and Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
Bioconjug Chem 18:773-84. 2007..Since the bioconjugates can also exhibit the attributes of passive targeting via enhanced permeability and retention, this is the first demonstration of a pivotal role of active targeting for immunotoxin bioconjugate efficacy...
New immunotoxins targeting CD123, a stem cell antigen on acute myeloid leukemia cellsXing Du
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4264, USA
J Immunother 30:607-13. 2007..In conclusion, 26292(Fv)-PE38-KDEL shows good cytotoxic activity against CD123 expressing cell lines, and merits further development for the possible treatment of acute myeloid leukemia and other CD123 expressing malignancies...
Immunotoxin and Taxol synergy results from a decrease in shed mesothelin levels in the extracellular space of tumorsYujian Zhang
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
Proc Natl Acad Sci U S A 104:17099-104. 2007....
In vitro and in vivo cytotoxic activities of recombinant immunotoxin 8H9(Fv)-PE38 against breast cancer, osteosarcoma, and neuroblastomaMasanori Onda
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute/NIH, 37 Convent Drive, Bethesda, MD 20892-4264, USA
Cancer Res 64:1419-24. 2004..These results make 8H9(dsFv)-PE38 a candidate for further development as a therapeutic agent for breast cancers, osteosarcomas, and neuroblastomas...
A guide to taming a toxin?-?recombinant immunotoxins constructed from Pseudomonas exotoxin A for the treatment of cancerJohn E Weldon
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
FEBS J 278:4683-700. 2011..This review summarizes our current understanding of PE, its intoxication pathway, and the ongoing efforts to convert this toxin into a treatment for cancer...
A primate-specific POTE-actin fusion protein plays a role in apoptosisXiu Fen Liu
National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4264, USA
Apoptosis 14:1237-44. 2009..Our data indicates that the POTE gene family encodes a new family of proapoptotic proteins...
The PATE gene is expressed in the accessory tissues of the human male genital tract and encodes a secreted sperm-associated proteinAngel A Soler-García
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 4264, USA
Reproduction 129:515-24. 2005....
Recombinant immunotoxins for treating cancerDavid J FitzGerald
Laboratory of Molecular Biology, CCR, National Cancer Institute, Bethesda, MD 20892, USA
Int J Med Microbiol 293:577-82. 2004..Candidate molecules with favorable characteristics are then evaluated in clinical trials. Here we report on the initial evaluation of BL22, a recombinant immunotoxin targeted to CD22 expressed on the surface of B-cell malignancies...
In vitro antibody affinity maturation targeting germline hotspotsMitchell Ho
National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Methods Mol Biol 525:293-308, xiv. 2009..Here, we describe procedures for germline hotspot mutagenesis with an emphasis on strategies for randomizing hotspots with PCR and phage display, using as an example the anti-CD22 monoclonal antibody...
DNA immunization followed by a single boost with cells: a protein-free immunization protocol for production of monoclonal antibodies against the native form of membrane proteinsSatoshi Nagata
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Dr, Rm 5106, Bethesda, MD 20892-4264, USA
J Immunol Methods 280:59-72. 2003..The large number of MAbs that react with high affinities to a variety of epitopes on the native form of antigens indicates that the method presented in this paper could be generally useful for generating MAbs to other membrane proteins...
Mammalian cell display for antibody engineeringMitchell Ho
National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Methods Mol Biol 525:337-52, xiv. 2009..Flow cytometry enhances the screen's sensitivity thereby allowing us to isolate high-affinity antibodies...
Inhibition of mesothelin-CA-125 interaction in patients with mesothelioma by the anti-mesothelin monoclonal antibody MORAb-009: Implications for cancer therapyRaffit Hassan
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4264, USA
Lung Cancer 68:455-9. 2010..MORAb-009 is a chimeric anti-mesothelin monoclonal antibody...
Identification of novel human CTL epitopes and their agonist epitopes of mesothelinJunko Yokokawa
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
Clin Cancer Res 11:6342-51. 2005..CONCLUSIONS: The identification of novel CTL agonist epitopes supports and extends observations that mesothelin is a potential target for immunotherapy of pancreatic and ovarian cancers, as well as mesotheliomas...
Approach to the patient after relapse of hairy cell leukemiaRobert J Kreitman
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Leuk Lymphoma 50:32-7. 2009..An improved high-affinity version of BL22, termed HA22, is currently undergoing phase I testing...
Characterization of T-cell repertoire in hairy cell leukemia patients before and after recombinant immunotoxin BL22 therapyEvgeny Arons
Laboratories of Molecular Biology and Pathology, and Biostatistics and Data Management Section, Centers for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Cancer Immunol Immunother 55:1100-10. 2006....
Non-AUG translational initiation of a short CAPC transcript generating protein isoformSuresh Anaganti
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Room 5110, Bethesda, MD 20892 4264, USA
Biochem Biophys Res Commun 380:508-13. 2009..5 kDa. N-terminal amino acid sequencing of the purified 7.5 kDa protein product indicated that translation starts at the codon for cysteine on the S..
In vitro antibody evolution targeting germline hot spots to increase activity of an anti-CD22 immunotoxinMitchell Ho
Laboratory of Molecular Biology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
J Biol Chem 280:607-17. 2005..Our results demonstrate that germline hot spots but not non-germline hot spots are effective for in vitro antibody affinity maturation...
A model for obesity and gigantism due to disruption of the Ankrd26 geneTapan K Bera
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4264, USA
Proc Natl Acad Sci U S A 105:270-5. 2008..These results show that alterations in an unidentified gene can lead to obesity and identify a molecular target for the treatment of obesity...
Selective elimination of human regulatory T lymphocytes in vitro with the recombinant immunotoxin LMB-2Peter Attia
Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
J Immunother (1997) 29:208-14. 2006..The short in vivo half-life of LMB-2 makes it an attractive candidate for reducing human T(reg) cells in vivo before the administration of cancer vaccine or cell transfer immunotherapy approaches...
Improved cytotoxic activity toward cell lines and fresh leukemia cells of a mutant anti-CD22 immunotoxin obtained by antibody phage displayGiuliana Salvatore
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-4264, USA
Clin Cancer Res 8:995-1002. 2002..The THW mutant had a 5- to 10-fold increase in activity on various CD22-positive cell lines and was up to 50 times more cytotoxic to cells from patients with chronic lymphocytic leukemia and hairy-cell leukemia...
Antibody fusion proteins: anti-CD22 recombinant immunotoxin moxetumomab pasudotoxRobert J Kreitman
Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland, USA
Clin Cancer Res 17:6398-405. 2011..Moreover, protein engineering is being used to increase its activity, decrease nonspecific side effects, and remove B-cell epitopes...
Recombinant immunotoxins and other therapies for relapsed/refractory hairy cell leukemiaRobert J Kreitman
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Leuk Lymphoma 52:82-6. 2011..In separate randomized trials, rituximab is undergoing phase II testing with cladribine for early HCL and with bendamustine or pentostatin for multiply relapsed HCL...
Phase I clinical trial of the chimeric anti-mesothelin monoclonal antibody MORAb-009 in patients with mesothelin-expressing cancersRaffit Hassan
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 4264, USA
Clin Cancer Res 16:6132-8. 2010..5 to 400 mg/m(2). Disease evaluation with computed tomography occurred on day 35. Subjects with responding or stable disease could receive additional cycles of MORAb-009...
Enhancing immunotoxin cell-killing activity via combination therapy with ABT-737David J FitzGerald
Laboratory of Molecular Biology, CCR, National Cancer Institute, NIH, HHS, Bethesda, MD, USA
Leuk Lymphoma 52:79-81. 2011..Expression of high levels of prosurvival Bcl-2 proteins may contribute to toxin resistance...
Administration of a CD25-directed immunotoxin, LMB-2, to patients with metastatic melanoma induces a selective partial reduction in regulatory T cells in vivoDaniel J Powell
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
J Immunol 179:4919-28. 2007....
Localization of mesothelin in epithelial ovarian cancerRaffit Hassan
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 4264, USA
Appl Immunohistochem Mol Morphol 13:243-7. 2005..Patients whose tumors express mesothelin could be eligible for participation in clinical trials of novel agents targeting mesothelin...
Phase I trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with B-cell malignanciesRobert J Kreitman
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bldg 5124b, 9000 Rockville Pike, Bethesda, MD 20892, USA
J Clin Oncol 23:6719-29. 2005..To conduct a phase I trial of recombinant immunotoxin BL22, an anti-CD22 Fv fragment fused to truncated Pseudomonas exotoxin...
Mesothelin: a new target for immunotherapyRaffit Hassan
Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland, USA
Clin Cancer Res 10:3937-42. 2004..There is evidence that mesothelin is an immunogenic protein and could be exploited as a therapeutic cancer vaccine. A soluble mesothelin variant has been identified and could be a useful tumor marker for malignant mesotheliomas...
Pretreatment with rituximab does not inhibit the human immune response against the immunogenic protein LMB-1Raffit Hassan
Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland, USA
Clin Cancer Res 10:16-8. 2004..The development of human antibodies against LMB-1 was detected using a serum neutralization and ELISA...
Immunotoxins containing Pseudomonas exotoxin A: a short historyIra Pastan
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, 37 Convent Drive, Room 5106, Bethesda, MD 20892-4268, USA
Cancer Immunol Immunother 52:338-41. 2003
Immunobiological treatments of hairy-cell leukaemiaRobert J Kreitman
Laboratory of Molecular Biology, Centers for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 37, Room 5106, Bethesda, MD 20892 4255, USA
Best Pract Res Clin Haematol 16:117-33. 2003..The unlabelled mAb rituximab has also been reported to induce responses in the majority of HCL patients treated, and several CRs have been observed...
Immunotoxins in cancer therapyIra Pastan
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4264, USA
Curr Opin Investig Drugs 3:1089-91. 2002..Unfortunately, most antibodies do not kill cancer cells unless they are armed with a cytotoxic agent, such as a radioisotope, a cytotoxic drug, or a protein toxin. Each of these have advantages and disadvantages...
Increased affinity and stability of an anti-HIV-1 envelope immunotoxin by structure-based mutagenesisLouise McHugh
Laboratory of Biochemistry, National Cancer Institute/National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892, USA
J Biol Chem 277:34383-90. 2002..Such site-directed mutants may increase the utility of immunotoxins for reducing or eradicating persistent HIV-1 infection in humans...
Generation and characterization of novel monoclonal antibodies to the Ret receptor tyrosine kinaseGiuliana Salvatore
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4264, USA
Biochem Biophys Res Commun 294:813-7. 2002....
BL22 and lymphoid malignanciesRobert J Kreitman
Centers for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 37, Room 5124b, Bethesda, MD 20892 4255, USA
Best Pract Res Clin Haematol 19:685-99. 2006..Already under way are a phase-II trial in HCL and phase-I trials in chronic lymphocytic leukemia (CLL) and acute lymphocytic leukemia (ALL) administering BL22 in a modified protocol in an effort to prevent HUS...
Phase I study of SS1P, a recombinant anti-mesothelin immunotoxin given as a bolus I.V. infusion to patients with mesothelin-expressing mesothelioma, ovarian, and pancreatic cancersRaffit Hassan
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute and Clinical Center, NIH, Bethesda, Maryland 20892 4264, USA
Clin Cancer Res 13:5144-9. 2007..To determine the toxicities, maximum tolerated dose (MTD) and pharmacokinetics of the recombinant immunotoxin SS1P (anti-mesothelin dsFv-PE38) in patients with mesothelin-expressing cancers...
Immunotoxins in the treatment of hematologic malignanciesRobert J Kreitman
Clinical Immunotherapy Section, Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 37, Room 5124b, Bethesda, MD 20892 4255, USA
Curr Drug Targets 7:1301-11. 2006..Several other recombinant immunotoxins are undergoing preclinical development for other target antigens expressed on hematologic malignancies...
Eradication of tumor colonization and invasion by a B cell-specific immunotoxin in a murine model for human primary intraocular lymphomaZhuqing Li
Laboratory of Immunology, National Eye Institute and Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
Cancer Res 66:10586-93. 2006..The results of B cell-specific immunotoxin therapy may have clinical implications in treating human PIOL...
Mutants of immunotoxin anti-Tac(dsFv)-PE38 with variable number of lysine residues as candidates for site-specific chemical modification. 1. Properties of mutant moleculesMasanori Onda
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Room 5106, Bethesda, Maryland 20892-4264, USA
Bioconjug Chem 14:480-7. 2003..Our data indicate that replacement of lysine residues can be achieve without loss of biological potency. These molecules are a useful starting point to carry out site-specific PEGylation experiments...
Cytotoxicity of the anti-CD22 immunotoxin HA22 (CAT-8015) against paediatric acute lymphoblastic leukaemiaFrancis Mussai
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4264, USA
Br J Haematol 150:352-8. 2010..These results provide a strong rationale for clinical testing of this agent in children with drug-resistant ALL and offers the potential to reduce morbidities of treatment while improving outcome...
Characterization of overlapping XAGE-1 transcripts encoding a cancer testis antigen expressed in lung, breast, and other types of cancersKristi A Egland
Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892 4264, USA
Mol Cancer Ther 1:441-50. 2002..Because XAGE-1 is expressed in such a diverse range of cancers, it has potential to be used as a target for many cancer immunotherapies...
Pseudomonas exotoxin A-mediated apoptosis is Bak dependent and preceded by the degradation of Mcl-1Xing Du
Laboratory of Molecular Biology, National Cancer Institute, 37 Convent Drive, Bethesda, MD 20892 4264, USA
Mol Cell Biol 30:3444-52. 2010..Overexpression of Mcl-1 and Bcl-x(L) inhibited PE-induced MEF death. Our data suggest that Bak is the preferential mediator of PE-mediated apoptosis and that the rapid degradation of Mcl-1 unleashes Bak to activate apoptosis...
Radioimmunotherapy of A431 xenografted mice with pretargeted B3 antibody-streptavidin and (90)Y-labeled 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA)-biotinZhengsheng Yao
Nuclear Medicine Department of the Warren G. Magnuson Clinical Center, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
Cancer Res 62:5755-60. 2002....
Recombinant immunotoxins in the treatment of cancerIra Pastan
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Methods Mol Biol 248:503-18. 2004
Lowering of pI by acylation improves the renal uptake of 99mTc-labeled anti-Tac dsFv: effect of different acylating reagentsInsook Kim
Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892-1180, USA
Nucl Med Biol 29:795-801. 2002..The reduced renal uptake was also reflected in the reduced whole-body retention, indicating that lowering the pI inhibited the tubular reabsorption of the labeled dsFv...
Antitumor activity of SS(dsFv)PE38 and SS1(dsFv)PE38, recombinant antimesothelin immunotoxins against human gynecologic cancers grown in organotypic culture in vitroRaffit Hassan
Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
Clin Cancer Res 8:3520-6. 2002..Our results also show low concentrations of an immunotoxin targeting mesothelin is cytotoxic to mesothelin-expressing human tumors by inducing apoptosis...
Targeted therapy against human lung cancer in nude mice by high-affinity recombinant antimesothelin single-chain Fv immunotoxinDominic Fan
Department of Cancer Biology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
Mol Cancer Ther 1:595-600. 2002..Our data indicate that mesothelin-producing squamous cell carcinoma of the lung may be a good target for this immunotoxin...
Preclinical evaluation of MORAb-009, a chimeric antibody targeting tumor-associated mesothelinRaffit Hassan
Morphotek Inc, 210 Welsh Pool Road, Exton, PA, USA
Cancer Immun 7:20. 2007..We have in fact initiated a Phase I clinical study enrolling patients with mesothelin-positive pancreatic, mesothelioma, non-small cell lung and ovarian cancers...
Mesothelin, a possible target for immunotherapy, is expressed in primary AML cellsDaniel Steinbach
University Children s Hospital Jena, Germany
Eur J Haematol 79:281-6. 2007..SS1(dsFv)PE38 is a recombinant anti-mesothelin immunotoxin which is undergoing clinical evaluation in patients with mesothelin-expressing tumors...
Induction of hyperintense signal on T2-weighted MR images correlates with infusion distribution from intracerebral convection-enhanced delivery of a tumor-targeted cytotoxinJohn H Sampson
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
AJR Am J Roentgenol 188:703-9. 2007..Our purpose was to test the hypothesis that hyperintense signal changes on T2-weighted images produced by such infusions can be used to track drug distribution...
Mesothelin-MUC16 binding is a high affinity, N-glycan dependent interaction that facilitates peritoneal metastasis of ovarian tumorsJennifer A A Gubbels
Department of Obstetrics and Gynecology, University of Wisconsin Madison, Madison, USA
Mol Cancer 5:50. 2006..Here we have addressed this deficit and provide further evidence supporting the role of the MUC16-mesothelin interaction in facilitating cell-cell binding under conditions that mimic the peritoneal environment...
Mesothelin is shed from tumor cellsMitchell Ho
Cancer Epidemiol Biomarkers Prev 15:1751. 2006
Anti-HIV-1 immunotoxin 3B3(Fv)-PE38: enhanced potency against clinical isolates in human PBMCs and macrophages, and negligible hepatotoxicity in macaquesPaul E Kennedy
Laboratory of Viral Diseases, NIAID, National Institutes of Health Building 4, Room 237 Bethesda, MD 20892, USA
J Leukoc Biol 80:1175-82. 2006..These findings highlight the potential use of 3B3(Fv)-PE38 for depleting HIV-infected cell reservoirs persisting in the face of HAART...
Identification of a set of seven genes for the monitoring of minimal residual disease in pediatric acute myeloid leukemiaDaniel Steinbach
University Children s Hospital Jena, Jena, Germany
Clin Cancer Res 12:2434-41. 2006..It is used for risk-adapted therapy and for the recognition of pending relapses. In acute myeloid leukemia (AML), there is still a need for more suitable MRD markers...
Differential cellular internalization of anti-CD19 and -CD22 immunotoxins results in different cytotoxic activityXing Du
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 4264, USA
Cancer Res 68:6300-5. 2008..Our results show that the rapid internalization of large amounts of BL22 bound to CD22 makes CD22 a better therapeutic target than CD19 for immunotoxins and probably for other immunoconjugates that act inside cells...
