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Immunotoxin Treatment Of Cancer.
I. Pastan, R. Hassan, D. Fitzgerald, R. Kreitman
Published 2007 · Biology, Medicine
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Immunotoxins are proteins used to treat cancer that are composed of an antibody fragment linked to a toxin. The immunotoxin binds to a surface antigen on a cancer cell, enters the cell by endocytosis, and kills it. The most potent immunotoxins are made from bacterial and plant toxins. Refinements over many years have produced recombinant immunotoxins; these therapeutic proteins are made using protein engineering. Individual immunotoxins are designed to treat specific cancers. To date, most success has been achieved treating hematologic tumors. Obstacles to successful treatment of solid tumors include poor penetration into tumor masses and the immune response to the toxin component of the immunotoxin, which limits the number of cycles that can be given. Strategies to overcome these limitations are being pursued.
This paper references
Low and high affinity cellular receptors for interleukin 2. Implications for the level of Tac antigen
R. Robb (1984)
A comparison of antilymphocyte immuno
A Bolognesi (1992)
Recombinant immunotoxins for treating cancer.
D. Fitzgerald (2004)
Targeting Pseudomonas exotoxin to hematologic malignancies.
R. Kreitman (1995)
Inhibition of TNF-α Produced by Kupffer Cells Protects Against the Nonspecific Liver Toxicity of Immunotoxin Anti-Tac(Fv)-PE38, LMB-2
M. Onda (2000)
Identification of Residues That Stabilize the Single-chain Fv of Monoclonal Antibodies B3 (*)
I. Benhar (1995)
Improving antibody affinity by mimicking somatic hypermutation in vitro
P. Chowdhury (1999)
Reduction of the nonspecific animal toxicity of anti-Tac(Fv)-PE38 by mutations in the framework regions of the Fv which lower the isoelectric point.
M. Onda (1999)
Phase I trial of a novel diphtheria toxin/granulocyte macrophage colony-stimulating factor fusion protein (DT388GMCSF) for refractory or relapsed acute myeloid leukemia.
A. Frankel (2002)
S. Takagi (1927)
Phase I trial of a ligand fusion-protein (DAB389IL-2) in lymphomas expressing the receptor for interleukin-2.
C. Lemaistre (1998)
Adjuvant therapy of stage III and IV malignant melanoma using granulocyte-macrophage colony-stimulating factor.
L. Spitler (2000)
Hairy cell leukemia, a B-cell neoplasm that is particularly sensitive to the cytotoxic effect of anti-Tac(Fv)-PE38 (LMB-2).
D. Robbins (2000)
Pseudomonas exotoxin-based immunotoxins containing the antibody LL2 or LL2-Fab' induce regression of subcutaneous human B-cell lymphoma in mice.
R. Kreitman (1993)
A phase I/II study of the intralesional injection of ricin-monoclonal antibody conjugates in patients with hepatic metastases.
J. Zalcberg (1994)
A phase-1 trial of bexarotene and denileukin diftitox in patients with relapsed or refractory cutaneous T-cell lymphoma.
F. Foss (2005)
A multicenter dose-escalation trial with denileukin diftitox (ONTAK, DAB(389)IL-2) in patients with severe psoriasis.
A. Martin (2001)
IL-2 receptor expression in human lymphoid lesions. Immunohistochemical study of 166 cases.
J. Strauchen (1987)
Clinical experience with denileukin diftitox (ONTAK).
F. Foss (2006)
Interleukin‐2 Fusion Toxin: Targeted Therapy for Cutaneous T Cell Lymphoma
F. Foss (2001)
Cleavage of pseudomonas exotoxin and diphtheria toxin by a furin-like enzyme prepared from beef liver.
M. Chiron (1994)
Characterization of monoclonal antibodies B1 and B3 that react with mucinous adenocarcinomas.
I. Pastan (1991)
Clinical evaluation of ricin A-chain immunotoxins in patients with Hodgkin's lymphoma.
R. Schnell (2003)
Mesothelin: a new target for immunotherapy.
R. Hassan (2004)
280 Updated results of the phase I study of SS1(dsFv)PE38 for targeted therapy of mesothelin expressing cancers
R. Hassan (2004)
Targeted induction of apoptosis by chimeric granzyme B fusion proteins carrying antibody and growth factor domains for cell recognition
B. Daelken (2006)
Improved cytotoxic activity
G Salvatore (2002)
Phase I trial of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) in patients with hematologic malignancies.
R. Kreitman (2000)
Hairy cell leukemia-variant treated with 2-chlorodeoxyadenosine--a report of three cases.
M. Błasińska-Morawiec (1997)
Antimelanoma monoclonal antibody ricin A and cyclophosphamide: potential therapeutic use in patients with malignant melanoma
Treatment of advanced solid tumors
LH Pai (1996)
Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma.
E. Olsen (2001)
Phase II clinical trial of bolus infusion anti-B4 blocked ricin immunoconjugate in patients with relapsed B-cell non-Hodgkin's lymphoma.
P. Multani (1998)
Recombinant single-chain immunotoxins against T and B cell leukemias.
R. Kreitman (1994)
Improved cytotoxic activity toward cell lines and fresh leukemia cells of a mutant anti-CD22 immunotoxin obtained by antibody phage display.
G. Salvatore (2002)
Anti‐B4‐blocked ricin: a phase II trial of 7 day continuous infusion in patients with multiple myeloma
M. Grossbard (1998)
Phase I study of monoclonal antibody-ricin A chain immunotoxin XomaZyme-791 in patients with metastatic colon cancer.
V. Byers (1989)
Phase II study of denileukin diftitox for relapsed/refractory B-Cell non-Hodgkin's lymphoma.
N. Dang (2004)
Taming ricin toxin
R. Kreitman (2003)
Phase I clinical study of the recombinant antibody toxin scFv(FRP5)-ETA specific for the ErbB2/HER2 receptor in patients with advanced solid malignomas
G. von Minckwitz (2005)
Efficacy of the anti-CD22 recombinant immunotoxin BL22 in chemotherapy-resistant hairy-cell leukemia.
R. Kreitman (2001)
Antitumor activity of Fab' and IgG-anti-CD22 immunotoxins in disseminated human B lymphoma grown in mice with severe combined immunodeficiency disease: effect on tumor cells in extranodal sites.
M. A. Ghetie (1991)
A phase II study of DT fusion protein denileukin diftitox in patients with fludarabine-refractory chronic lymphocytic leukemia.
A. Frankel (2003)
Interleukin 2 receptor-targeted cytotoxicity. Interleukin 2 receptor- mediated action of a diphtheria toxin-related interleukin 2 fusion protein
P. Bacha (1988)
Serotherapy of B-cell neoplasms with anti-B4-blocked ricin: a phase I trial of daily bolus infusion.
M. Grossbard (1992)
Phase I Study of Monoclonal Antibody‐Ricin A Chain Immunoconjugate Xomazyme‐791 in Patients with Metastatic Colon Cancer
P. LoRusso (1995)
Delivery of Molecular Medicine to Solid Tumors
R. Jain (1996)
Phase I evaluation of an anti-breast carcinoma monoclonal antibody 260F9-recombinant ricin A chain immunoconjugate.
L. Weiner (1989)
B3(Fv)-PE38KDEL, a single-chain immunotoxin that causes complete regression of a human carcinoma in mice.
U. Brinkmann (1991)
Evaluation of ricin A chain-containing immunotoxins directed against CD19 and CD22 antigens on normal and malignant human B-cells as potential reagents for in vivo therapy.
M. A. Ghetie (1988)
Hairy cell leukemia-variant.
I. Al-Sheikh (2001)
Single-dose murine monoclonal antibody ricin A chain immunotoxin in the treatment of metastatic melanoma: a phase I trial.
R. González (1991)
Immunotoxin therapy of small-cell lung cancer: a phase I study of N901-blocked ricin.
T. Lynch (1997)
Immunotoxin combined with chemotherapy for patients with AIDS‐related non‐Hodgkin's lymphoma
D. Scadden (1998)
Genetic engineering of an immunotoxin to eliminate pulmonary vascular leak in mice
Joan E. Smallshaw (2003)
Anti-B4-blocked ricin: a phase I trial of 7-day continuous infusion in patients with B-cell neoplasms.
M. Grossbard (1993)
A Phase I study with an anti-CD30 ricin A-chain immunotoxin (Ki-4.dgA) in patients with refractory CD30+ Hodgkin's and non-Hodgkin's lymphoma.
R. Schnell (2002)
Expression and purification of the recombinant diphtheria fusion toxin DT388IL3 for phase I clinical trials.
J. O. Urieto (2004)
Adjuvant immunotoxin therapy with anti-B4-blocked ricin after autologous bone marrow transplantation for patients with B-cell non-Hodgkin's lymphoma.
M. Grossbard (1993)
Phase I/II study of murine monoclonal antibody-ricin A chain (XOMAZYME-Mel) immunoconjugate plus cyclosporine A in patients with metastatic melanoma.
K. Selvaggi (1993)
Evaluation of a CD25-specific immunotoxin for prevention of graft-versus-host disease after unrelated marrow transplantation.
P. Martin (2004)
Diphtheria toxin fused to human interleukin-3 is toxic to blasts from patients with myeloid leukemias
A. Frankel (2000)
Complete regression of human fibrosarcoma xenografts after local Newcastle disease virus therapy.
R. Lorence (1994)
Ki-4(scFv)-ETA', a new recombinant anti-CD30 immunotoxin with highly specific cytotoxic activity against disseminated Hodgkin tumors in SCID mice.
S. Barth (2000)
Remodeling domain interfaces to enhance heterodimer formation
Z. Zhu (1997)
Pharmacokinetics of the recombinant fusion protein DAB486IL-2 in animal models
P. Bacha (2008)
[Hairy cell leukemia].
H. Loeffler (1976)
A comparison of anti‐lymphocyte immunotoxins containing different ribosome‐inactivating proteins and antibodies
A. Bolognesi (1992)
A phase II study of the immunotoxin N901-blocked ricin in small-cell lung cancer.
P. Fidias (2002)
Cellular processing of the interleukin-2 fusion toxin DAB486-IL-2 and efficient delivery of diphtheria fragment A to the cytosol of target cells requires Arg194.
D. Williams (1990)
Hepatotoxicity in cancer patients receiving erb-38, a recombinant immunotoxin that targets the erbB2 receptor.
L. Pai-Scherf (1999)
Targeted induction of apoptosis for cancer therapy
E. Bremer (2006)
The natural history and clinico-pathological features of the variant form of hairy cell leukemia
E. Matutes (2001)
Complete regression of human B‐cell lymphoma xenografts in mice treated with recombinant anti‐CD22 immunotoxin RFB4(dsFv)‐PE38 at doses tolerated by cynomolgus monkeys
R. Kreitman (1999)
A urokinase-activated recombinant diphtheria toxin targeting the granulocyte-macrophage colony-stimulating factor receptor is selectively cytotoxic to human acute myeloid leukemia blasts.
R. Abi-Habib (2004)
selectively cytotoxic to human acute myeloid leukemia blasts granulocyte-macrophage colony-stimulating factor receptor is A urokinase-activated recombinant diphtheria toxin targeting the
R. Abi-Habib (2009)
The 150th Anniversary of the Birth of Charlotte Brontë
Donald G. Hopewell (1966)
An anti-CD30 single-chain Fv selected by phage display and fused to Pseudomonas exotoxin A (Ki-4(scFv)-ETÁ) is a potent immunotoxin against a Hodgkin-derived cell line
A. Klimka (1999)
Immunotoxins and vascular leak syndrome.
E. Vitetta (2000)
Lineage specific treatment of adult patients with acute lymphoblastic leukemia in first remission with anti‐B4‐blocked ricin or high‐dose cytarabine
T. Szatrowski (2003)
Phase I study of an anti-breast cancer immunotoxin by continuous infusion: report of a targeted toxic effect not predicted by animal studies.
B. Gould (1989)
Pharmacokinetics of In-111- and I-125labeled antiTac single-chain Fv recombinant immunotoxin
H Kobayashi (2000)
Phase I study of an antibreast cancer
BJ Gould (1989)
Quality-of-life improvements in cutaneous T-cell lymphoma patients treated with denileukin diftitox (ONTAK).
M. Duvic (2002)
Treatment of refractory Hodgkin's lymphoma patients with an anti-CD25 ricin A-chain immunotoxin
R. Schnell (2000)
Pharmacokinetics of 111In- and 125I-labeled antiTac single-chain Fv recombinant immunotoxin.
H. Kobayashi (2000)
A phase I study of an anti-CD22-deglycosylated ricin A chain immunotoxin in the treatment of B-cell lymphomas resistant to conventional therapy.
P. Amlot (1993)
Accumulation of a recombinant immunotoxin in a tumor in vivo: fewer than 1000 molecules per cell are sufficient for complete responses.
R. Kreitman (1998)
T. Connors (1974)
Specifically targeting the CD22 receptor of human B-cell lymphomas with RNA damaging agents.
D. Newton (2001)
Synergistic Antitumor Activity of Taxol and Immunotoxin SS1P in Tumor-Bearing Mice
Y. Zhang (2006)
Selective Elimination of Human Regulatory T Lymphocytes In Vitro With the Recombinant Immunotoxin LMB-2
Peter Attia (2006)
A recombinant immunotoxin consisting of two antibody variable domains fused to Pseudomonas exotoxin
Vijay K. Chaudhary (1989)
Antimelanoma monoclonal antibody-ricin A chain immunoconjugate (XMMME-001-RTA) plus cyclophosphamide in the treatment of metastatic malignant melanoma: results of a phase II trial.
R. Oratz (1990)
Chemical construction of immunotoxins
V. Ghetie (2001)
Regression of Cutaneous Tumor Lesions in Patients Intratumorally Injected with a Recombinant Single-chain Antibody-toxin Targeted to ErbB2/HER2
M. Azémar (2004)
Clinical evaluation of intraperitoneal Pseudomonas exotoxin immunoconjugate OVB3-PE in patients with ovarian cancer.
L. Pai (1991)
Cytotoxic activity of disulfide-stabilized recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) toward fresh malignant cells from patients with B-cell leukemias.
R. Kreitman (2000)
Continuous infusion of the anti-CD22 immunotoxin IgG-RFB4-SMPT-dgA in patients with B-cell lymphoma: a phase I study.
E. Sausville (1995)
Responses in refractory hairy cell leukemia to a recombinant immunotoxin.
R. Kreitman (1999)
Recombinant immunotoxins containing anti-Tac(Fv) and derivatives of Pseudomonas exotoxin produce complete regression in mice of an interleukin-2 receptor-expressing human carcinoma
R. Kreitman (1994)
Combination chemotherapy followed by an immunotoxin (anti-B4-blocked ricin) in patients with indolent lymphoma: results of a phase II study.
D. Longo (2000)
Interleukin‐2 Receptor β‐Chain (p70–75) Expressed on Leukemic Cells from Adult T Cell Leukemia Patients
T. Kodaka (1990)
A phase I trial of the single-chain immunotoxin SGN-10 (BR96 sFv-PE40) in patients with advanced solid tumors.
J. Posey (2002)
A phase I study of combination therapy with immunotoxins IgG-HD37-deglycosylated ricin A chain (dgA) and IgG-RFB4-dgA (Combotox) in patients with refractory CD19(+), CD22(+) B cell lymphoma.
R. Messmann (2000)
Novel anti-CD30 recombinant immunotoxins containing disulfide-stabilized Fv fragments.
Satoshi Nagata (2002)
B-cell restricted saporin immunotoxins: activity against B-cell lines and chronic lymphocytic leukemia cells.
M. Bregni (1989)
Demonstration of high-affinity interleukin-2 receptors on B-chronic lymphocytic leukemia cells: Functional and structural characterization
H. Yagura (2005)
Denileukin diftitox for the treatment of panniculitic lymphoma.
Karen S. McGinnis (2002)
Isolation of new anti‐CD30 scFvs from DNA‐immunized mice by phage display and biologic activity of recombinant immunotoxins produced by fusion with truncated pseudomonas exotoxin
H. Rozemuller (2001)
Phase I trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with B-cell malignancies.
R. Kreitman (2005)
Interleukin-2 receptor b-chain
T Kodaka (1990)
A Phase II study of adjuvant therapy with anti-B4-blocked ricin after autologous bone marrow transplantation for patients with relapsed B-cell non-Hodgkin's lymphoma.
M. Grossbard (1999)
Phase I Trial of Intravenous IL-4 Pseudomonas Exotoxin Protein (NBI-3001) in Patients with Advanced Solid Tumors That Express the IL-4 Receptor
L. Garland (2005)
[Phase I clinical study].
H. Majima (1984)
Phase I trial of a novel matrix metalloproteinase inhibitor batimastat (BB-94) in patients with advanced cancer
S. Wojtowicz-Praga (2004)
Specifically Targeting the CD22 Receptor of Human B-cell Lymphomas with RNA Damaging Agents: A New Generation of Therapeutics
M. Hursey (2002)
Treatment of advanced solid tumors with immunotoxin LMB–1: An antibody linked to Pseudomonas exotoxin
L. Pai (1996)
This paper is referenced by
Mesothelin-Targeted Agents in Clinical Trials and in Preclinical Development
R. Kelly (2012)
Improving the therapeutic potential of human granzyme B and evaluation of granzyme M as novel effector molecules in cytolytic fusion proteins for the treatment of Serpin B9-positive cancer
S. Schiffer (2014)
RECOMBINANT EXPRESSION AND PURIFICATION OF PSEUDOMONAS AERUGINOSA TRUNCATED EXOTOXIN A IN ESCHERICHIA COLI
B. Behzad (2013)
HER2-specific recombinant immunotoxin 4D5scFv-PE40 passes through retrograde trafficking route and forces cells to enter apoptosis
Evgeniya A Sokolova (2017)
Current advances and outlooks in immunotherapy for pancreatic ductal adenocarcinoma
Jia-qiao Fan (2020)
Ricin and Saporin: Plant Enzymes for the Research and the Clinics
F. Giansanti (2010)
An immunotoxin with greatly reduced immunogenicity by identification and removal of B cell epitopes
M. Onda (2008)
Challenging the roles of CD44 and lipolysis stimulated lipoprotein receptor in conveying Clostridium perfringens iota toxin cytotoxicity in breast cancer
K. Fagan-Solis (2014)
Photochemical internalization of recombinant toxins targeting EGFR and HER2 for treatment of aggressive and resistant cancers
M. Berstad (2015)
Inclusion of a Furin Cleavage Site Enhances Antitumor Efficacy against Colorectal Cancer Cells of Ribotoxin α-Sarcin- or RNase T1-Based Immunotoxins
J. Ruiz-de-la-Herrán (2019)
Production of unique immunotoxin cancer therapeutics in algal chloroplasts
M. Tran (2012)
Therapeutic and diagnostic Nanobodies and their application in veterinary medicine
Sophie-Louise Georges (2019)
The characterisation of a recombinant cytosolic shuttle based on ricin toxin
A. Kotha (2011)
Recombinant adenovirus IL-24-Bax promotes apoptosis of hepatocellular carcinoma cells in vitro and in vivo
J. Li (2010)
Preclinical evaluation of VB6-845: an anti-EpCAM immunotoxin with reduced immunogenic potential.
J. Entwistle (2012)
Improved immunotoxins with novel functional elements.
C. Hetzel (2009)
An EGFR/HER2-Bispecific and Enediyne-Energized Fusion Protein Shows High Efficacy against Esophageal Cancer
Xiao-fang Guo (2014)
Establishment of a three-step purification scheme for a recombinant protein rG17PE38 and its characteristics identification.
X. Feng (2015)
Discovery and Characterization of Novel ADP-Ribosylating Toxins
R. Fieldhouse (2011)
Preclinical assessment of an anti-EpCAM immunotoxin: locoregional delivery provides a safer alternative to systemic administration.
J. Brown (2009)
Monoclonal antibody-based therapies in cancer: advances and challenges.
P. Sapra (2013)
Antibody-based Therapeutics for the Treatment of Human B cell Malignancies
S. Baskar (2012)
In vivo imaging of immunotoxin treatment using Katushka-transfected A-431 cells in a murine xenograft tumour model
A. Pardo (2012)
T-Cell Receptor-Like Antibodies: Targeting the Intracellular Proteome Therapeutic Potential and Clinical Applications
M. Cohen (2013)
Anti‐tumor activity of a B‐cell receptor‐targeted peptide in a novel disseminated lymphoma xenograft model
C. Wehr (2012)
The Use of Plant-Derived Ribosome Inactivating Proteins in Immunotoxin Development: Past, Present and Future Generations
Aleksander Rust (2017)
Recombinant immunotoxins and other therapies for relapsed/refractory hairy cell leukemia
R. Kreitman (2011)
Prospects of bacterial and plant protein-based immunotoxins for treatment of cancer.
U. Weidle (2014)
Development of a platform technology for enhanced endo/lysosomal escape of targeted toxins by structurally specific oleanane saponins
Roger Gilabert-Oriol (2014)
Enhancing immunotoxin cell-killing activity via combination therapy with ABT-737
D. Fitzgerald (2011)
Investigation of HIV cure strategies in vivo in BLT humanized mice
Perry Tsai (2016)
Photochemical internalization (PCI) of immunotoxins directed against putative cancer stem cell markers in triple-negative breast cancer and malignant melanoma
M. S. Eng (2012)See more