Attempts to Express the A1-GMCSF Immunotoxin in the Baculovirus Expression Vector System

Jahanian-Najafabadi, Ali; Bouzari, Saeid; Oloomi, Mana; Roudkenar, Mehryar Habibi; Mayr, Lorenz M.

doi:10.1271/bbb.110862

Cited by 6 publications

(3 citation statements)

References 30 publications

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“…In the former strategy, tumor-specific receptors, which are not, or are much less, expressed on normal cells are targeted by a monoclonal antibody, or an antibody fragment, which consequently blocks ligand–receptor interaction and intracellular signaling ( 10 ). Furthermore, the antibody/antibody fragment or the ligand can also be fused to a protein toxin to specifically kill the targeted cancer cell.…”

Section: Introductionmentioning

confidence: 99%

Pseudomonas Exotoxin-Based Immunotoxins: Over Three Decades of Efforts on Targeting Cancer Cells With the Toxin

2021

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Cancer is one of the prominent causes of death worldwide. Despite the existence of various modalities for cancer treatment, many types of cancer remain uncured or develop resistance to therapeutic strategies. Furthermore, almost all chemotherapeutics cause a range of side effects because they affect normal cells in addition to malignant cells. Therefore, the development of novel therapeutic agents that are targeted specifically toward cancer cells is indispensable. Immunotoxins (ITs) are a class of tumor cell-targeted fusion proteins consisting of both a targeting moiety and a toxic moiety. The targeting moiety is usually an antibody/antibody fragment or a ligand of the immune system that can bind an antigen or receptor that is only expressed or overexpressed by cancer cells but not normal cells. The toxic moiety is usually a protein toxin (or derivative) of animal, plant, insect, or bacterial origin. To date, three ITs have gained Food and Drug Administration (FDA) approval for human use, including denileukin diftitox (FDA approval: 1999), tagraxofusp (FDA approval: 2018), and moxetumomab pasudotox (FDA approval: 2018). All of these ITs take advantage of bacterial protein toxins. The toxic moiety of the first two ITs is a truncated form of diphtheria toxin, and the third is a derivative of Pseudomonas exotoxin (PE). There is a growing list of ITs using PE, or its derivatives, being evaluated preclinically or clinically. Here, we will review these ITs to highlight the advances in PE-based anticancer strategies, as well as review the targeting moieties that are used to reduce the non-specific destruction of non-cancerous cells. Although we tried to be as comprehensive as possible, we have limited our review to those ITs that have proceeded to clinical trials and are still under active clinical evaluation.

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Section: Introductionmentioning

confidence: 99%

Pseudomonas Exotoxin-Based Immunotoxins: Over Three Decades of Efforts on Targeting Cancer Cells With the Toxin

2021

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“…The toxic moieties of immunotoxins have been derived from bacterial, fungal, plant, and even animal toxins (Cao et al, 2012; Weidle et al, 2014), while growth factors, monoclonal antibodies, cytokines (Aruna, 2006), and cancer-specific cell-penetrating peptides (CPPs) (Kersemans and Cornelissen, 2010; Soleimani et al, 2016, 2019) have been used as targeting moieties. Of the bacterial toxins, Vibrio cholerae toxin (Sarnovsky et al, 2010), Shiga toxin (Al-Jaufy et al, 1994; Jahanian-Najafabadi et al, 2012a), Pseudomonas exotoxin A (Yu et al, 2017; Dhillon, 2018), and DT (Vallera et al, 1999; Liu et al, 2000; Vaclavkova et al, 2006) have been used as either an immunotoxin or some other form of targeted toxin. Among these, DT is the most widely used due to its easy expression, high activity, and minimal side effects in humans (Brinkmann et al, 1995).…”

Section: Immunotoxinsmentioning

confidence: 99%

Targeted Diphtheria Toxin-Based Therapy: A Review Article

Shafiee¹,

Aucoin²,

Jahanian-Najafabadi³

2019

Front. Microbiol.

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Cancer remains one of the leading causes of death worldwide. Conventional therapeutic strategies usually offer limited specificity, resulting in severe side effects and toxicity to normal tissues. Targeted cancer therapy, on the other hand, can improve the therapeutic potential of anti-cancer agents and decrease unwanted side effects. Targeted applications of cytolethal bacterial toxins have been found to be especially useful for the specific eradication of cancer cells. Targeting is either mediated by peptides or by protein-targeting moieties, such as antibodies, antibody fragments, cell-penetrating peptides (CPPs), growth factors, or cytokines. Together with a toxin domain, these molecules are more commonly referred to as immunotoxins. Targeting can also be achieved through gene delivery and cell-specific expression of a toxin. Of the available cytolethal toxins, diphtheria toxin (DT) is one of the most frequently used for these strategies. Of the many DT-based therapeutic strategies investigated to date, two immunotoxins, OntakTM and TagraxofuspTM, have gained FDA approval for clinical application. Despite some success with immunotoxins, suicide-gene therapy strategies, whereby controlled tumor-specific expression of DT is used for the eradication of malignant cells, are gaining prominence. The first part of this review focuses on DT-based immunotoxins, and it then discusses recent developments in tumor-specific expression of DT.

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“…Since BEVS is based on eukaryotic protein expression machinery and secretes recombinant proteins in a soluble form, proteins necessary for maintaining natural protein conformation have been produced with high purity and functionality [ 29 , 30 , 31 ]. To date, several bacterial and eukaryotic toxin molecules have been successfully purified using BEVS [ 31 , 32 , 33 , 34 ]; however, to the best of our knowledge, no studies have reported the use of BEVS to produce recombinant wild-type SEB.…”

Section: Introductionmentioning

confidence: 99%

A Sensitive Immunodetection Assay Using Antibodies Specific to Staphylococcal Enterotoxin B Produced by Baculovirus Expression

Jang

Kim

et al. 2022

Biosensors

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Staphylococcal enterotoxin B (SEB) is a potent bacterial toxin that causes inflammatory stimulation and toxic shock, thus it is necessary to detect SEB in food and environmental samples. Here, we developed a sensitive immunodetection system using monoclonal antibodies (mAbs). Our study is the first to employ a baculovirus expression vector system (BEVS) to produce recombinant wild-type SEB. BEVS facilitated high-quantity and pure SEB production from suspension-cultured insect cells, and the SEB produced was characterized by mass spectrometry analysis. The SEB was stable at 4 °C for at least 2 years, maintaining its purity, and was further utilized for mouse immunization to generate mAbs. An optimal pair of mAbs non-competitive to SEB was selected for sandwich enzyme-linked immunosorbent assay-based immunodetection. The limit of detection of the immunodetection method was 0.38 ng/mL. Moreover, it displayed higher sensitivity in detecting SEB than commercially available immunodetection kits and retained detectability in various matrices and S. aureus culture supernatants. Thus, the results indicate that BEVS is useful for producing pure recombinant SEB with its natural immunogenic property in high yield, and that the developed immunodetection assay is reliable and sensitive for routine identification of SEB in various samples, including foods.

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Attempts to Express the A1-GMCSF Immunotoxin in the Baculovirus Expression Vector System

Cited by 6 publications

References 30 publications

Pseudomonas Exotoxin-Based Immunotoxins: Over Three Decades of Efforts on Targeting Cancer Cells With the Toxin

Pseudomonas Exotoxin-Based Immunotoxins: Over Three Decades of Efforts on Targeting Cancer Cells With the Toxin

Targeted Diphtheria Toxin-Based Therapy: A Review Article

A Sensitive Immunodetection Assay Using Antibodies Specific to Staphylococcal Enterotoxin B Produced by Baculovirus Expression

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