Scholars

NIH Distinguished Investigator

Positions:

NIH Distinguished Investigator, Laboratory of Molecular Biology

Research Areas:

Research & Experimental Medicine, Engineering, Genetics & Heredity, Food Science & Technology, Rheumatology, Science & Technology - Other Topics, Cardiovascular System & Cardiology, Biophysics, Pharmacology & Pharmacy, Radiology, Nuclear Medicine & Medical Imaging, Pediatrics, Anatomy & Morphology, Reproductive Biology, Endocrinology & Metabolism, Biochemistry & Molecular Biology, Oncology, Materials Science, Microbiology, Respiratory System, Cell Biology, Chemistry, Obstetrics & Gynecology, Hematology, Biotechnology & Applied Microbiology, Transplantation, Urology & Nephrology, Physiology, Immunology, Neurosciences & Neurology, Virology, Medical Laboratory Technology, Parasitology, Pathology, Toxicology

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Research Areas:

overview

Dr. Pastan is co-chief of the Laboratory of Molecular Biology, Center for Cancer Research. He obtained his M.D. from Tufts University, received his medical training at Yale University and research training at the NIH. He established the Laboratory of Molecular Biology in 1970.

selected publications

Articles1

(2020). Enhanced efficacy of mesothelin-targeted immunotoxin LMB-100 and anti-PD-1 antibody in patients with mesothelioma and mouse tumor models. Science Translational Medicine. 12(550),

Academic Articles1201

(2020). Phase 1 study of the immunotoxin LMB-100 in patients with mesothelioma and other solid tumors expressing mesothelin. CANCER. 126(22), 4936-4947.
(2020). Development of Recombinant Immunotoxins for Hairy Cell Leukemia. 10(8),
(2020). Enhanced efficacy of mesothelin-targeted immunotoxin LMB-100 and anti-PD-1 antibody in patients with mesothelioma and mouse tumor models. Science Translational Medicine. 12(550),
(2020). Population pharmacokinetics, efficacy, and safety of moxetumomab pasudotox in patients with relapsed or refractory hairy cell leukaemia. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY. 86(7), 1367-1376.
(2020). Phase I/II Study of the Mesothelin-targeted Immunotoxin LMB-100 with Nab-Paclitaxel for Patients with Advanced Pancreatic Adenocarcinoma. CLINICAL CANCER RESEARCH. 26(4), 828-836.
(2020). Engineered Anti-GPC3 Immunotoxin, HN3-ABD-T20, Produces Regression in Mouse Liver Cancer Xenografts Through Prolonged Serum Retention. HEPATOLOGY. 71(5), 1696-1711.
(2020). Contextualizing the Use of Moxetumomab Pasudotox in the Treatment of Relapsed or Refractory Hairy Cell Leukemia. ONCOLOGIST. 25(1), E170-E177.
(2019). Anti-BCMA immunotoxins produce durable complete remissions in two mouse myeloma models. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 116(10), 4592-4598.
(2019). Depletion of regulatory T cells in tumors with an anti-CD25 immunotoxin induces CD8 T cell-mediated systemic antitumor immunity. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA.
(2019). Diphthamide affects selenoprotein expression: Diphthamide deficiency reduces selenocysteine incorporation, decreases selenite sensitivity and pre-disposes to oxidative stress. Redox Biology. 20, 146-156.
(2019). Generation of a Transgenic BALB/c Mouse Line With Selective Expression of Human Mesothelin in Thyroid Gland: Application in Mesothelin-targeted Immunotherapy. JOURNAL OF IMMUNOTHERAPY. 42(4), 119-125.
(2019). Global polysome analysis of normal and injured podocytes. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY. 316(2), F241-F252.
(2019). Improved efficacy against malignant brain tumors with EGFRwt/EGFRvIII targeting immunotoxin and checkpoint inhibitor combinations. Journal for ImmunoTherapy of Cancer. 7,
(2019). Interplay between reversible phosphorylation and irreversible ADP-ribosylation of eukaryotic translation elongation factor 2. BIOLOGICAL CHEMISTRY. 400(4), 501-512.
(2019). Possible role of complement factor H in podocytes in clearing glomerular subendothelial immune complex deposits. Scientific Reports. 9,
(2019). Pseudomonas Exotoxin Immunotoxins and Anti-Tumor Immunity: From Observations at the Patient's Bedside to Evaluation in Preclinical Models. Toxins. 11(1),
(2019). Synergistic antitumor effects of 9.2.27-PE38KDEL and ABT-737 in primary and metastatic brain tumors. PLoS One. 14(1),
(2018). 5-Azacytidine prevents relapse and produces long-term complete remissions in leukemia xenografts treated with Moxetumomab pasudotox. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 115(8), E1867-E1875.
(2018). Anti-drug antibodies to LMB-100 are enhanced by mAbs targeting OX40 and CTLA4 but not by mAbs targeting PD1 or PDL-1. CELLULAR IMMUNOLOGY. 334, 38-41.
(2018). Cancer vaccine strategies: translation from mice to human clinical trials. CANCER IMMUNOLOGY IMMUNOTHERAPY. 67(12), 1863-1869.
(2018). Domain II of Pseudomonas Exotoxin Is Critical for Efficacy of Bolus Doses in a Xenograft Model of Acute Lymphoblastic Leukemia. Toxins. 10(5),
(2018). Elevated Serum Megakaryocyte Potentiating Factor as a Predictor of Poor Survival in Patients with Mesothelioma and Primary Lung Cancer. 3(2), 166-177.
(2018). Improving the In Vivo Efficacy of an Anti-Tac (CD25) Immunotoxin by Pseudomonas Exotoxin A Domain II Engineering. MOLECULAR CANCER THERAPEUTICS. 17(7), 1486-1493.
(2018). Interactions Between Pseudomonas Immunotoxins and the Plasma Membrane: Implications for CAT-8015 Immunotoxin Therapy. Frontiers in Oncology. 8,
(2018). Low-Dose Methotrexate Prevents Primary and Secondary Humoral Immune Responses and Induces Immune Tolerance to a Recombinant Immunotoxin. JOURNAL OF IMMUNOLOGY. 200(6), 2038-2045.
(2018). Megakaryocyte Potentiating Factor as a Predictive Biomarker for Therapies Against Malignant Mesothelioma. 2, 1-16.
(2018). Minimal residual hairy cell leukemia eradication with moxetumomab pasudotox: phase 1 results and long-term follow-up. BLOOD. 131(21), 2331-2334.
(2018). Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia. LEUKEMIA. 32(8), 1768-1777.
(2018). Recombinant immunotoxins targeting B-cell maturation antigen are cytotoxic to myeloma cell lines and myeloma cells from patients. LEUKEMIA. 32(2), 569-572.
(2018). Recombinant immunotoxins with albumin-binding domains have long half-lives and high antitumor activity. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA.
(2018). SS1P Immunotoxin Induces Markers of Immunogenic Cell Death and Enhances the Effect of the CTLA-4 Blockade in AE17M Mouse Mesothelioma Tumors. Toxins. 10(11),
(2018). Strategies to Reduce the Immunogenicity of Recombinant Immunotoxins. AMERICAN JOURNAL OF PATHOLOGY. 188(8), 1736-1743.
(2018). Tolerogenic nanoparticles restore the antitumor activity of recombinant immunotoxins by mitigating immunogenicity. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 115(4), E733-E742.
(2017). 5'UTR point substitutions and N-terminal truncating mutations of ANKRD26 in acute myeloid leukemia. Journal of Hematology & Oncology. 10,
(2017). Combining Local Immunotoxins Targeting Mesothelin with CTLA-4 Blockade Synergistically Eradicates Murine Cancer by Promoting Anticancer Immunity. Cancer Immunology Research. 5(8), 685-694.
(2017). Comprehensive immunohistochemical study of mesothelin (MSLN) using different monoclonal antibodies 5B2 and MN-1 in 1562 tumors with evaluation of its prognostic value in malignant pleural mesothelioma. 8(16), 26744-26754.
(2017). Construction of an immunotoxin, HN3-mPE24, targeting glypican-3 for liver cancer therapy. 8(20), 32450-32460.
(2017). Efficacy of Anti-mesothelin Immunotoxin RG7787 plus Nab-Paclitaxel against Mesothelioma Patient-Derived Xenografts and Mesothelin as a Biomarker of Tumor Response. CLINICAL CANCER RESEARCH. 23(6), 1564-1574.
(2017). Elimination of murine and human T-cell epitopes in recombinant immunotoxin eliminates neutralizing and anti-drug antibodies in vivo. Cellular & Molecular Immunology. 14(5), 432-442.
(2017). Paclitaxel synergizes with exposure time adjusted CD22-targeting immunotoxins against B-cell malignancies. 8(19), 30644-30655.
(2017). Panbinostat decreases cFLIP and enhances killing of cancer cells by immunotoxin LMB-100 by stimulating the extrinsic apoptotic pathway. 8(50), 87307-87316.
(2017). Phase 1 study of the anti-CD22 immunotoxin moxetumomab pasudotox for childhood acute lymphoblastic leukemia. BLOOD. 130(14), 1620-1627.
(2017). Production and quality control assessment of a GLP-grade immunotoxin, D2C7-(scdsFv)-PE38KDEL, for a phase I/II clinical trial. APPLIED MICROBIOLOGY AND BIOTECHNOLOGY. 101(7), 2747-2766.
(2017). Rational design of low immunogenic anti CD25 recombinant immunotoxin for T cell malignancies by elimination of T cell epitopes in PE38. CELLULAR IMMUNOLOGY. 313, 59-66.
(2017). Role of HLA-DP in the Presentation of Epitopes from the Truncated Bacterial PE38 Immunotoxin. AAPS Journal. 19(1), 117-129.
(2017). Specific CpG hyper-methylation leads to Ankrd26 gene downregulation in white adipose tissue of a mouse model of diet-induced obesity. Scientific Reports. 7,
(2017). Tubulointerstitial fibrosis can sensitize the kidney to subsequent glomerular injury. KIDNEY INTERNATIONAL. 92(6), 1395-1403.
(2016). 3D Culture Supports Long-Term Expansion of Mouse and Human Nephrogenic Progenitors. Cell Stem Cell. 19(4), 516-529.
(2016). Actinomycin D enhances killing of cancer cells by immunotoxin RG7787 through activation of the extrinsic pathway of apoptosis. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 113(38), 10666-10671.
(2016). Anti-TGF-beta Antibody, 1D11, Ameliorates Glomerular Fibrosis in Mouse Models after the Onset of Proteinuria. PLoS One. 11(5),
(2016). Anticancer Effects of Mesothelin-Targeted Immunotoxin Therapy Are Regulated by Tyrosine Kinase DDR1. CANCER RESEARCH. 76(6), 1560-1568.
(2016). Characterization of a re-engineered, mesothelin-targeted Pseudomonas exotoxin fusion protein for lung cancer therapy. Molecular Oncology. 10(8), 1317-1329.
(2016). Chemical Screens Identify Drugs that Enhance or Mitigate Cellular Responses to Antibody-Toxin Fusion Proteins. PLoS One. 11(8),
(2016). Complete Remissions of Adult T-cell Leukemia with Anti-CD25 Recombinant Immunotoxin LMB-2 and Chemotherapy to Block Immunogenicity. CLINICAL CANCER RESEARCH. 22(2), 310-318.
(2016). Dual B- and T-cell de-immunization of recombinant immunotoxin targeting mesothelin with high cytotoxic activity. 7(21), 29916-29926.
(2016). Expression of mesothelin in thymic carcinoma and its potential therapeutic significance. LUNG CANCER. 101, 104-110.
(2016). Immunogenicity of therapeutic recombinant immunotoxins. IMMUNOLOGICAL REVIEWS. 270(1), 152-164.
(2016). Mesothelin Expression in Advanced Gastroesophageal Cancer Represents a Novel Target for Immunotherapy. APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY. 24(4), 246-252.
(2016). Mesothelin Immunotherapy for Cancer: Ready for Prime Time?. JOURNAL OF CLINICAL ONCOLOGY. 34(34), 4171-+.
(2016). New Life for Immunotoxin Cancer Therapy. CLINICAL CANCER RESEARCH. 22(5), 1055-1058.
(2016). Preclinical toxicity evaluation of a novel immunotoxin, D2C7-(scdsFv)-PE38KDEL, administered via intracerebral convection-enhanced delivery in rats. INVESTIGATIONAL NEW DRUGS. 34(2), 149-158.
(2016). Protection of the Furin Cleavage Site in Low-Toxicity Immunotoxins Based on Pseudomonas Exotoxin A..
(2016). Protein Kinase Inhibitor H89 Enhances the Activity of Pseudomonas Exotoxin A-Based Immunotoxins. MOLECULAR CANCER THERAPEUTICS. 15(5), 1053-1062.
(2016). Ranking Differential Drug Activities from Dose-Response Synthetic Lethality Screens. 21(9), 942-955.
(2016). Reduced Shedding of Surface Mesothelin Improves Efficacy of Mesothelin-Targeting Recombinant Immunotoxins. MOLECULAR CANCER THERAPEUTICS. 15(7), 1648-1655.
(2016). TARP vaccination is associated with slowing in PSA velocity and decreasing tumor growth rates in patients with Stage D0 prostate cancer. OncoImmunology. 5(8),
(2016). Wide Variability in the Time Required for Immunotoxins to Kill B Lineage Acute Lymphoblastic Leukemia Cells: Implications for Trial Design. CLINICAL CANCER RESEARCH. 22(19), 4913-4922.
(2015). A novel form of ciliopathy underlies hyperphagia and obesity in Ankrd26 knockout mice. Brain Structure & Function. 220(3), 1511-1528.
(2015). Advances in Anticancer Immunotoxin Therapy. ONCOLOGIST. 20(2), 176-185.
(2015). Bortezomib Reduces Pre-Existing Antibodies to Recombinant Immunotoxins in Mice. JOURNAL OF IMMUNOLOGY. 194(4), 1695-1701.
(2015). Characterization of CD22 Expression in Acute Lymphoblastic Leukemia. PEDIATRIC BLOOD & CANCER. 62(6), 964-969.
(2015). Designing the Furin-Cleavable Linker in Recombinant Immunotoxins Based on Pseudomonas Exotoxin A. BIOCONJUGATE CHEMISTRY. 26(6), 1120-1128.
(2015). Engineering NK Cells Modified With an EGFRvIII-specific Chimeric Antigen Receptor to Overexpress CXCR4 Improves Immunotherapy of CXCL12/SDF-1 alpha-secreting Glioblastoma. JOURNAL OF IMMUNOTHERAPY. 38(5), 197-210.
(2015). High mesothelin expression in advanced lung adenocarcinoma is associated with KRAS mutations and a poor prognosis. Oncotarget. 6(13), 11694-11702.
(2015). Immunoconjugates in the management of hairy cell leukemia. BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY. 28(4), 236-245.
(2015). Loss of diphthamide pre-activates NF-kappa B and death receptor pathways and renders MCF7 cells hypersensitive to tumor necrosis factor. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 112(34), 10732-10737.
(2015). Mesothelioma patient derived tumor xenografts with defined BAP1 mutations that mimic the molecular characteristics of human malignant mesothelioma. BMC CANCER. 15,
(2015). Methylation-Associated Partial Down-Regulation of Mesothelin Causes Resistance to Anti-Mesothelin Immunotoxins in a Pancreatic Cancer Cell Line. PLoS One. 10(3),
(2015). New High Affinity Monoclonal Antibodies Recognize Non-Overlapping Epitopes On Mesothelin For Monitoring And Treating Mesothelioma. Scientific Reports. 5,
(2015). Podocyte Injury-Driven Lipid Peroxidation Accelerates the Infiltration of Glomerular Foam Cells in Focal Segmental Glomerulosclerosis. AMERICAN JOURNAL OF PATHOLOGY. 185(8), 2118-2131.
(2015). Podocyte injury-driven intracapillary plasminogen activator inhibitor type 1 accelerates podocyte loss via uPAR-mediated beta(1)-integrin endocytosis. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY. 308(6), F614-F626.
(2015). Poor correlation between T-cell activation assays and HLA-DR binding prediction algorithms in an immunogenic fragment of Pseudomonas exotoxin A. JOURNAL OF IMMUNOLOGICAL METHODS. 425, 10-20.
(2015). Quantification of recombinant immunotoxin delivery to solid tumors allows for direct comparison of in vivo and in vitro results. Scientific Reports. 5,
(2015). Recombinant Immunotoxin with T-cell Epitope Mutations That Greatly Reduce Immunogenicity for Treatment of Mesothelin-Expressing Tumors. MOLECULAR CANCER THERAPEUTICS. 14(12), 2789-2796.
(2015). Safety and biodistribution of In-111-amatuximab in patients with mesothelin expressing cancers using Single Photon Emission Computed Tomography-Computed Tomography (SPECT-CT) imaging. Oncotarget. 6(6), 4496-4504.
(2015). The Role of Multidrug Resistance Efflux Pumps in Cancer: Revisiting a JNCI Publication Exploring Expression of the MDR1 (P-glycoprotein) Gene. JNCI-Journal of the National Cancer Institute. 107(9),
(2015). Tumor and organ uptake of Cu-64-labeled MORAb-009 (amatuximab), an anti-mesothelin antibody, by PET imaging and biodistribution studies. NUCLEAR MEDICINE AND BIOLOGY. 42(11), 880-886.
(2015). Unilateral ureteral obstruction attenuates intrarenal angiotensin II generation induced by podocyte injury. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY. 308(8), F932-F937.
(2015). Whole-genome RNAi screen highlights components of the endoplasmic reticulum/Golgi as a source of resistance to immunotoxin-mediated cytotoxicity. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 112(10), E1135-E1142.
(2014). An improved recombinant Fab-immunotoxin targeting CD22 expressing malignancies. LEUKEMIA RESEARCH. 38(10), 1224-1229.
(2014). Antitumor Effects of Immunotoxins Are Enhanced by Lowering HCK or Treatment with Src Kinase Inhibitors. MOLECULAR CANCER THERAPEUTICS. 13(1), 82-89.
(2014). CD21(-/low) Marginal Zone B Cells Highly Express Fc Receptor-like 5 Protein and Are Killed by Anti-Fc Receptor-like 5 Immunotoxins in Hepatitis C Virus-Associated Mixed Cryoglobulinemia Vasculitis. Arthritis & Rheumatology. 66(2), 433-443.
(2014). Class II human leucocyte antigen DRB1*11 in hairy cell leukaemia patients with and without haemolytic uraemic syndrome. BRITISH JOURNAL OF HAEMATOLOGY. 166(5), 729-738.
(2014). Combining the Antimesothelin Immunotoxin SS1P With the BH3-mimetic ABT-737 Induces Cell Death in SS1P-resistant Pancreatic Cancer Cells. JOURNAL OF IMMUNOTHERAPY. 37(1), 8-15.
(2014). Discovery of Mesothelin and Exploiting It as a Target for Immunotherapy. CANCER RESEARCH. 74(11), 2907-2912.
(2014). Effect of Antigen Shedding on Targeted Delivery of Immunotoxins in Solid Tumors from a Mathematical Model. PLoS One. 9(10),
(2014). Efficacy of RG7787, a Next-Generation Mesothelin-Targeted Immunotoxin, against Triple-Negative Breast and Gastric Cancers. MOLECULAR CANCER THERAPEUTICS. 13(11), 2653-2661.
(2014). Immunotoxins for leukemia. BLOOD. 123(16), 2470-2477.
(2014). In Vitro and In Vivo Activity of the Low-Immunogenic Antimesothelin Immunotoxin RG7787 in Pancreatic Cancer. MOLECULAR CANCER THERAPEUTICS. 13(8), 2040-2049.
(2014). Keap1 inhibition attenuates glomerulosclerosis. NEPHROLOGY DIALYSIS TRANSPLANTATION. 29(4), 783-791.

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Articles1

Academic Articles1201