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Immunotoxins: Current Status and Future Perspectives

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Special Issue Editor

Dr. Salvatore Giovanni De Simone

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Guest Editor

Center for Technological Development in Healthy, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil
Interests: protein; peptide biochemistry

Special Issue Information

Dear Colleagues,

Immunotoxins can be of animal, plant, bacterial, viral, or other origin. These molecules are the result of a genetic or biochemical manipulation (chimera) that involves the binding of antibodies (whole or smaller segments) to a naturally toxic substance. Immunotoxins have the function of binding to receptors on the surface of target cells and exerting their deadly or therapeutic biological effect. One of the main applications of immunotoxins is in oncology. Cancer cells frequently upregulate surface receptors that promote growth and survival. These receptors constitute valid targets for intervention. One therapeutic strategy involves the delivery of toxic payloads to kill the cancer cells with high receptor levels. Delivery can be accomplished by attaching a toxic load to either a receptor-binding antibody or a receptor-binding ligand. Generally, the cell-binding domain of the toxin is replaced with a ligand or antibody that dictates a new binding specificity. The advantage of this "immunotoxin" approach lies in the potency of these chimeric molecules for killing cancer cells. However, receptor expression on normal tissue represents a significant obstacle to therapeutic intervention.

We are pleased to invite you to submit your work to “Immunotoxins: Current Status and Future Perspectives” that I am organizing in the journal Toxins (ISSN 2072-6651, IF 4.546). This Special Issue aims to provide a platform for toxicologists, molecular pharmacologists, molecular immunologists, life science researchers, doctors, clinicians, researchers, and other professionals to understand the recent advancements and challenges in immunotoxins research. Suggested themes and article types for submissions include antibody–toxin conjugates; monoclonal antibodies; epitope target identification; antibody–drug conjugates; immunoliposomes; therapeutic use; drug targeting; targeted therapy; construction of molecules; delivery; mechanism of action and resistance; clinical application; cancer (pancreatic adenocarcinoma, liver cancer; hairy cell leukemia and others); as well as cholera toxin, dianthin, trichosanthin, and mesothelin. In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to): cancer; COVID-19; animal venoms; bacterial toxins; marine and freshwater toxins; mycotoxins; plant toxins; uremic toxins; chimeric molecules; antibodies; and others.

We look forward to your contribution.

Dr. Salvatore Giovanni De Simone
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

immunotoxins
antibody–toxin conjugate
targeted therapy
construction of molecules
delivery
mechanism of action and resistance
clinical application
cancer
pancreatic adenocarcinoma
hepatocellular carcinoma
liver cancer
COVID-19

Published Papers (2 papers)

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Research

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17 pages, 4303 KiB

Open AccessArticle

High-Throughput IgG Epitope Mapping of Tetanus Neurotoxin: Implications for Immunotherapy and Vaccine Design

by Salvatore G. De-Simone, Paloma Napoleão-Pêgo, Guilherme C. Lechuga, João P. R. S. Carvalho, Larissa R. Gomes, Sergian V. Cardozo, Carlos M. Morel, David W. Provance, Jr. and Flavio R. da Silva

Toxins 2023, 15(4), 239; https://doi.org/10.3390/toxins15040239 - 24 Mar 2023

Cited by 1 | Viewed by 1893

Abstract

Tetanus is an acute, fatal disease caused by exotoxins released from Clostridium tetani during infections. A protective humoral immune response can be induced by vaccinations with pediatric and booster combinatorial vaccines that contain inactivated tetanus neurotoxin (TeNT) as a major antigen. Although some epitopes in TeNT have been described using various approaches, a comprehensive list of its antigenic determinants that are involved with immunity has not been elucidated. To this end, a high-resolution analysis of the linear B-cell epitopes in TeNT was performed using antibodies generated in vaccinated children. Two hundred sixty-four peptides that cover the entire coding sequence of the TeNT protein were prepared in situ on a cellulose membrane through SPOT synthesis and probed with sera from children vaccinated (ChVS) with a triple DTP-vaccine to map continuous B-cell epitopes, which were further characterized and validated using immunoassays. Forty-four IgG epitopes were identified. Four (TT-215-218) were chemically synthesized as multiple antigen peptides (MAPs) and used in peptide ELISAs to screen post-pandemic DTP vaccinations. The assay displayed a high performance with high sensitivity (99.99%) and specificity (100%). The complete map of linear IgG epitopes induced by vaccination with inactivated TeNT highlights three key epitopes involved in the efficacy of the vaccine. Antibodies against epitope TT-8/G can block enzymatic activity, and those against epitopes TT-41/G and TT-43/G can interfere with TeNT binding to neuronal cell receptors. We further show that four of the epitopes identified can be employed in peptide ELISAs to assess vaccine coverage. Overall, the data suggest a set of select epitopes to engineer new, directed vaccines. Full article

(This article belongs to the Special Issue Immunotoxins: Current Status and Future Perspectives)

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Review

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39 pages, 4591 KiB

Open AccessReview

Hosts and Heterologous Expression Strategies of Recombinant Toxins for Therapeutic Purposes

by Luana di Leandro, Martina Colasante, Giuseppina Pitari and Rodolfo Ippoliti

Toxins 2023, 15(12), 699; https://doi.org/10.3390/toxins15120699 - 13 Dec 2023

Viewed by 1715

Abstract

The production of therapeutic recombinant toxins requires careful host cell selection. Bacteria, yeast, and mammalian cells are common choices, but no universal solution exists. Achieving the delicate balance in toxin production is crucial due to potential self-intoxication. Recombinant toxins from various sources find applications in antimicrobials, biotechnology, cancer drugs, and vaccines. “Toxin-based therapy” targets diseased cells using three strategies. Targeted cancer therapy, like antibody–toxin conjugates, fusion toxins, or “suicide gene therapy”, can selectively eliminate cancer cells, leaving healthy cells unharmed. Notable toxins from various biological sources may be used as full-length toxins, as plant (saporin) or animal (melittin) toxins, or as isolated domains that are typical of bacterial toxins, including Pseudomonas Exotoxin A (PE) and diphtheria toxin (DT). This paper outlines toxin expression methods and system advantages and disadvantages, emphasizing host cell selection’s critical role. Full article

(This article belongs to the Special Issue Immunotoxins: Current Status and Future Perspectives)

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