4.7 Review

Antibody-Based Immunotoxins for Colorectal Cancer Therapy

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Summary: The ImmunoPeCa trial investigated intraperitoneal MOC31PE immunotoxin as a novel therapeutic approach for peritoneal metastasis from colorectal cancer. The long-term outcomes showed promising results with high survival rates and potential benefits for certain patients with favorable characteristics. Further investigations into the clinical efficacy are supported by the study's findings.
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A bispecific immunotoxin (IHPP) with a long half-life targeting HER2 and PDGFRβ exhibited improved efficacy against HER2-positive tumors in a mouse xenograft model

Rui Guo et al.

Summary: Multiple signaling pathways are involved in tumor development, making bispecific antibodies more suitable for treating complex tumor diseases. A novel PE-based bispecific immunotoxin designed in this study showed improved efficacy against HER2-positive tumors. Transcriptome sequencing and real-time PCR were used to verify the results, indicating the potential of these bispecific immunotoxins for anti-HER2 cancer therapeutics.

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Novel EGFR-bispecific recombinant immunotoxin based on cucurmosin shows potent anti-tumor efficiency in vitro

Caiyun Zhang et al.

Summary: The study demonstrated the successful development of a novel targeting EGFR recombinant immunotoxin Bs/cucurmosin (CUS), which exhibited high selective cytotoxicity towards cells in vitro. Bs/CUS killed cells through the apoptosis pathway, making it a promising candidate for cancer therapy targeting EGFR-positive tumors.

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Immunotoxin IHP25-BT with low immunogenicity and off-target toxicity inhibits the growth and metastasis of trastuzumab-resistant tumor cells

Rui Guo et al.

Summary: The study generated two trastuzumab-resistant HER2-positive tumor cell populations and examined the anti-tumor effects of newly constructed immunotoxins with low immunogenicity and off-target toxicity based on these resistant tumor cells both in vitro and in vivo. Results showed that the immunotoxin not only effectively inhibited tumor growth, but also suppressed liver metastasis of tumor cells in a mouse xenograft model. Transciptome sequencing of tumor tissue was performed to elucidate the potential mechanisms of inhibiting tumor cell distant metastasis by immunotoxin, highlighting their promise for trastuzumab-resistant cancer therapy.

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Plant-made immunotoxin building blocks: A roadmap for producing therapeutic antibody-toxin fusions

M. Knoedler et al.

Summary: Molecular farming in plants is becoming a competitive platform for producing pharmaceutical proteins, with advantages in cost and technology over established hosts like bacteria and mammalian cells. Plants can produce a variety of recombinant therapeutic proteins, including replacement enzymes, vaccines, and monoclonal antibodies, and this review focuses on the production of active antibody-toxin fusion proteins (RITs) in plants.

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Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review

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Advancements in mRNA Encoded Antibodies for Passive Immunotherapy

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Summary: The study constructed a novel T cell-engaging bispecific antibody targeting Lewis Y and CD3, showing high affinity and anti-tumor activity against gastric cancer in vitro and in vivo. It demonstrated stronger T cell recruiting, activation, proliferation, cytokine release, and cytotoxicity compared to the parent monoclonal antibody, indicating potential therapeutic efficacy for gastric cancer.

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Engineered mRNA and the Rise of Next-Generation Antibodies

Laura Sanz et al.

Summary: Using gene transfer methods for in vivo secretion of therapeutic antibodies can avoid production and purification challenges, achieving sustained concentrations and benefitting short-lived antibody fragments and next-generation, Fc-free, multispecific antibodies.

ANTIBODIES (2021)

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Critical Issues in the Development of Immunotoxins for Anticancer Therapy

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Production of a Granulysin-Based, Tn-Targeted Cytolytic Immunotoxin Using Pulsed Electric Field Technology

Patricia Guerrero-Ochoa et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

Review Biochemistry & Molecular Biology

Targeting Receptors on Cancer Cells with Protein Toxins

Antonella Antignani et al.

BIOMOLECULES (2020)

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The Role of Cholesterol on Triterpenoid Saponin-Induced Endolysosomal Escape of a Saporin-Based Immunotoxin

Wendy S. Smith et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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RNA-electroporated T cells for cancer immunotherapy

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ONCOIMMUNOLOGY (2020)

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Comprehensive review of targeted therapy for colorectal cancer

Yuan-Hong Xie et al.

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Depletion of regulatory T cells in tumors with an anti-CD25 immunotoxin induces CD8 T cell-mediated systemic antitumor immunity

Masanori Onda et al.

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Anti-Mesothelin Recombinant Immunotoxin Therapy for Colorectal Cancer

Adam Cerise et al.

CLINICAL COLORECTAL CANCER (2019)

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Targeting EGFR pathway in metastatic colorectal cancer- tumour heterogeniety and convergent evolution

Khurum Khan et al.

CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY (2019)

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Evelien Dekker et al.

LANCET (2019)

Review Biochemistry & Molecular Biology

Hosts for Hostile Protein Production: The Challenge of Recombinant Immunotoxin Expression

Stefania Zuppone et al.

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Primary T cells for mRNA-mediated immunotoxin delivery

R. Eggers et al.

GENE THERAPY (2018)

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Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia

Robert J. Kreitman et al.

LEUKEMIA (2018)

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Recombinant immunotoxins with albumin-binding domains have long half-lives and high antitumor activity

Junxia Wei et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2018)

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Strategies to Improve the Clinical Utility of Saporin-Based Targeted Toxins

Francesco Giansanti et al.

TOXINS (2018)

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Bouganin, an Attractive Weapon for Immunotoxins

Massimo Bortolotti et al.

TOXINS (2018)

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Immunotoxins Targeting B cell Malignancy-Progress and Problems With Immunogenicity

Daniel A. Vallera et al.

BIOMEDICINES (2018)

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Updates in the Development of ImmunoRNases for the Selective Killing of Tumor Cells

Sandra Jordaan et al.

BIOMEDICINES (2018)

Review Biochemistry & Molecular Biology

Human Granzyme B Based Targeted Cytolytic Fusion Proteins

Precious Hlongwane et al.

BIOMEDICINES (2018)

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Immunotoxins in cancer therapy: Review and update

Bahman Akbari et al.

INTERNATIONAL REVIEWS OF IMMUNOLOGY (2017)

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Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade

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SCIENCE (2017)

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Fungal Ribotoxins: A Review of Potential Biotechnological Applications

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Recent advances in cancer drug discovery targeting RAS

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Epidermal growth factor receptor-targeted therapy in colorectal cancer

WeiDong Xu et al.

FRONTIERS IN BIOSCIENCE-LANDMARK (2016)

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Immunogenicity of therapeutic recombinant immunotoxins

Ronit Mazor et al.

IMMUNOLOGICAL REVIEWS (2016)

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Killer lymphocytes use granulysin, perforin and granzymes to kill intracellular parasites

Farokh Dotiwala et al.

NATURE MEDICINE (2016)

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How Do Cytotoxic Lymphocytes Kill Cancer Cells?

Luis Martinez-Lostao et al.

CLINICAL CANCER RESEARCH (2015)

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The coming of age of engineered multivalent antibodies

Natalia Nunez-Prado et al.

DRUG DISCOVERY TODAY (2015)

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Preparation of an engineered safer immunotoxin against colon carcinoma based on the ribotoxin hirsutellinA

Jaime Tome-Amat et al.

FEBS JOURNAL (2015)

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In vivo potential of recombinant granulysin against human tumors

Sameer Al-Wasaby et al.

ONCOIMMUNOLOGY (2015)

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Microencapsulation of therapeutic bispecific antibodies producing cells: immunotherapeutic organoids for cancer management

Laura Saenz del Burgo et al.

JOURNAL OF DRUG TARGETING (2015)

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Glycosylation in cancer: mechanisms and clinical implications

Salome S. Pinho et al.

NATURE REVIEWS CANCER (2015)

Review Biochemistry & Molecular Biology

Challenges in Antibody Development against Tn and Sialyl-Tn Antigens

Liliana R. Loureiro et al.

BIOMOLECULES (2015)

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Perforin and granzymes: function, dysfunction and human pathology

Ilia Voskoboinik et al.

NATURE REVIEWS IMMUNOLOGY (2015)

Article Chemistry, Multidisciplinary

Combination of antibody targeting and PTD-mediated intracellular toxin delivery for colorectal cancer therapy

Meong Cheol Shin et al.

JOURNAL OF CONTROLLED RELEASE (2014)

Article Oncology

EpCAM-Selective Elimination of Carcinoma Cells by a Novel MAP-Based Cytolytic Fusion Protein

Dmitrij Hristodorov et al.

MOLECULAR CANCER THERAPEUTICS (2014)

Review Oncology

The development of immunoconjugates for targeted cancer therapy

Brandon G. Smaglo et al.

NATURE REVIEWS CLINICAL ONCOLOGY (2014)

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The ErbB/HER family of protein-tyrosine kinases and cancer

Robert Roskoski

PHARMACOLOGICAL RESEARCH (2014)

Article Genetics & Heredity

Antibody Gene Therapy: Getting Closer to Clinical Application?

Irene Guijarro-Munoz et al.

CURRENT GENE THERAPY (2013)

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Panitumumab-FOLFOX4 Treatment and RAS Mutations in Colorectal Cancer

Jean-Yves Douillard et al.

NEW ENGLAND JOURNAL OF MEDICINE (2013)

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Production and characterization of scFvA33T1, an immunoRNase targeting colon cancer cells

Jaime Tome-Amat et al.

FEBS JOURNAL (2012)

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Production and characterization of a colon cancer-specific immunotoxin based on the fungal ribotoxin -sarcin

Nelson Carreras-Sangra et al.

PROTEIN ENGINEERING DESIGN & SELECTION (2012)

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Antibody-Based Immunotoxins for the Treatment of Cancer

Nurit Becker et al.

ANTIBODIES (2012)

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The Tn Antigen-Structural Simplicity and Biological Complexity

Tongzhong Ju et al.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2011)

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EGFR-targeted therapy

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EXPERIMENTAL CELL RESEARCH (2011)

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An Immunoconjugate of Anti-CD24 and Pseudomonas Exotoxin Selectively Kills Human Colorectal Tumors in Mice

Shiran Shapira et al.

GASTROENTEROLOGY (2011)

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124I-huA33 Antibody Uptake Is Driven by A33 Antigen Concentration in Tissues from Colorectal Cancer Patients Imaged by Immuno-PET

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JOURNAL OF NUCLEAR MEDICINE (2011)

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Initial characterization of an immunotoxin constructed from domains II and III of cholera exotoxin

Robert Sarnovsky et al.

CANCER IMMUNOLOGY IMMUNOTHERAPY (2010)

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A33 Antigen-Deficient Mice Have Defective Colonic Mucosal Repair

Prue M. Pereira-Fantini et al.

INFLAMMATORY BOWEL DISEASES (2010)

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Synergistic anti-cancer effects of immunotoxin and cyclosporin in vitro and in vivo

Y. Andersson et al.

BRITISH JOURNAL OF CANCER (2009)

Review Pharmacology & Pharmacy

Current Constructs and Targets in Clinical Development for Antibody-Based Cancer Therapy

P. M. Deckert

CURRENT DRUG TARGETS (2009)

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A33 antigen displays persistent surface expression

Margaret E. Ackerman et al.

CANCER IMMUNOLOGY IMMUNOTHERAPY (2008)

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From ImmunoToxins to ImmunoRNases

Claudia Lorenzo et al.

CURRENT PHARMACEUTICAL BIOTECHNOLOGY (2008)

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Antibody-targeted RNase fusion proteins (ImmunoRNases) for cancer therapy

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CURRENT PHARMACEUTICAL BIOTECHNOLOGY (2008)

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An immunotoxin with greatly reduced immunogenicity by identification and removal of B cell epitopes

Masanori Onda et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2008)

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Granzyme B-induced cell death exerted by ex vivo CTL:: discriminating requirements for cell death and some of its signs

J. Pardo et al.

CELL DEATH AND DIFFERENTIATION (2008)

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Immunotoxin treatment of cancer

Ira Pastan et al.

ANNUAL REVIEW OF MEDICINE (2007)

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Fungal ribotoxins: molecular dissection of a family of natural killers

Javier Lacadena et al.

FEMS MICROBIOLOGY REVIEWS (2007)

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In vitro and in vivo characterization of 177Lu-huA33 A radioimmunoconjugate against colorectal cancer

Ylva Almqvist et al.

NUCLEAR MEDICINE AND BIOLOGY (2006)

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CEACAMs: their role in physiology and pathophysiology

Katharina Kuespert et al.

CURRENT OPINION IN CELL BIOLOGY (2006)

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Immunotoxin therapy of cancer

Ira Pastan et al.

NATURE REVIEWS CANCER (2006)

Article Biochemistry & Molecular Biology

Cholesterol in negatively charged lipid bilayers modulates the effect of the antimicrobial protein granulysin

Hanna Barman et al.

JOURNAL OF MEMBRANE BIOLOGY (2006)

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Granulysin

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CURRENT OPINION IN IMMUNOLOGY (2003)

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Granulysin crystal structure and a structure-derived lytic mechanism

DH Anderson et al.

JOURNAL OF MOLECULAR BIOLOGY (2003)

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Analysis of the regulation of the A33 antigen gene reveals intestine-specific mechanisms of gene expression.

CN Johnstone et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2002)

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A distinct pathway of cell-mediated apoptosis initiated by granulysin

AA Kaspar et al.

JOURNAL OF IMMUNOLOGY (2001)