Special Issue "Toxins and Cancer Therapy"

A special issue of Toxins (ISSN 2072-6651).

Deadline for manuscript submissions: 31 January 2020.

Special Issue Editor

Dr. Adam E. Snook
E-Mail Website
Guest Editor
Department of Pharmacology & Experimental Therapeutics, Sidney Kimmel Medical College, Thomas Jefferson University
Interests: Immunotoxins; Cancer Immunology; Cancer Biology; Immunotherapy

Special Issue Information

Cancer is the second leading cause of death globally and is expected to become an increasing health, social, and economic burden over the coming decades as industrial lifestyles become more prevalent around the world. Approaches to cancer therapy have relied primarily on the selective toxicity of anticancer drugs. Indeed, more than 100 years ago, William Coley, a surgeon at Memorial Hospital in New York, was injecting patients with live bacteria and bacterial products to treat their cancers, often producing remarkable results, especially when treating sarcomas. “Coley’s Toxins” in their original form are no longer used, but the principles Coley began to uncover in the 1890s have evolved into our modern armamentarium for the treatment of cancer. The immunological mechanisms exploited by Coley and uncovered by a century of basic and clinical research have led to the development of remarkable new cancer immunotherapies—between 2015–2018 alone, 46 new cancer immunotherapy indications were approved by the US FDA. Moreover, while Coley’s treatments were often toxic, modern therapies selectively deliver toxic agents to tumors, using targeted radiotherapy, immunotoxins, and nanodelivery systems. Modern approaches even include bacterial enterotoxins, bacteria, and oncolytic viruses to prevent or treat cancer. Together, these therapies are transforming clinical cancer care, but their continued development and new discoveries are needed to ultimately address our growing need for safe and effective cancer therapies over the coming decades.

Keywords

  • Cancer
  • Immunotoxins
  • Immunotherapy
  • Radiotherapy
  • Nanodelivery
  • Bacteria
  • Oncolytic viruses
  • Enterotoxin

Published Papers (2 papers)

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Research

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Open AccessArticle
Inclusion of a Furin Cleavage Site Enhances Antitumor Efficacy against Colorectal Cancer Cells of Ribotoxin α-Sarcin- or RNase T1-Based Immunotoxins
Toxins 2019, 11(10), 593; https://doi.org/10.3390/toxins11100593 - 12 Oct 2019
Abstract
Immunotoxins are chimeric molecules that combine the specificity of an antibody to recognize and bind tumor antigens with the potency of the enzymatic activity of a toxin, thus, promoting the death of target cells. Among them, RNases-based immunotoxins have arisen as promising antitumor [...] Read more.
Immunotoxins are chimeric molecules that combine the specificity of an antibody to recognize and bind tumor antigens with the potency of the enzymatic activity of a toxin, thus, promoting the death of target cells. Among them, RNases-based immunotoxins have arisen as promising antitumor therapeutic agents. In this work, we describe the production and purification of two new immunoconjugates, based on RNase T1 and the fungal ribotoxin α-sarcin, with optimized properties for tumor treatment due to the inclusion of a furin cleavage site. Circular dichroism spectroscopy, ribonucleolytic activity studies, flow cytometry, fluorescence microscopy, and cell viability assays were carried out for structural and in vitro functional characterization. Our results confirm the enhanced antitumor efficiency showed by these furin-immunotoxin variants as a result of an improved release of their toxic domain to the cytosol, favoring the accessibility of both ribonucleases to their substrates. Overall, these results represent a step forward in the design of immunotoxins with optimized properties for potential therapeutic application in vivo. Full article
(This article belongs to the Special Issue Toxins and Cancer Therapy)
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Review

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Open AccessReview
Botulinum Neurotoxins and Cancer—A Review of the Literature
Toxins 2020, 12(1), 32; https://doi.org/10.3390/toxins12010032 (registering DOI) - 05 Jan 2020
Abstract
Botulinum neurotoxins (BoNT) possess an analgesic effect through several mechanisms including an inhibition of acetylcholine release from the neuromuscular junction as well as an inhibition of specific pain transmitters and mediators. Animal studies have shown that a peripheral injection of BoNTs impairs the [...] Read more.
Botulinum neurotoxins (BoNT) possess an analgesic effect through several mechanisms including an inhibition of acetylcholine release from the neuromuscular junction as well as an inhibition of specific pain transmitters and mediators. Animal studies have shown that a peripheral injection of BoNTs impairs the release of major pain transmitters such as substance P, calcitonin gene related peptide (CGRP) and glutamate from peripheral nerve endings as well as peripheral and central neurons (dorsal root ganglia and spinal cord). These effects lead to pain relief via the reduction of peripheral and central sensitization both of which reflect important mechanisms of pain chronicity. This review provides updated information about the effect of botulinum toxin injection on local pain caused by cancer, painful muscle spasms from a remote cancer, and pain at the site of cancer surgery and radiation. The data from the literature suggests that the local injection of BoNTs improves muscle spasms caused by cancerous mass lesions and alleviates the post-operative neuropathic pain at the site of surgery and radiation. It also helps repair the parotid damage (fistula, sialocele) caused by facial surgery and radiation and improves post-parotidectomy gustatory hyperhidrosis. The limited literature that suggests adding botulinum toxins to cell culture slows/halts the growth of certain cancer cells is also reviewed and discussed. Full article
(This article belongs to the Special Issue Toxins and Cancer Therapy)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

CNF1 Variants Endowed with the Ability to Cross the Blood-Brain Barrier: A New Potential Therapeutic Strategy for Glioblastoma

Andrea Colarusso, Zaira Maroccia, Ermenegilda Parrilli, Elena Germinario, Maria Luisa Tutino, 
Carla Fiorentini and Alessia Fabbri

Abstract: Gliomas are primary tumours occurring in the central nervous system that arise from glial cells. According to the recent World Health Organization classification, glioblastoma or glioblastoma multiforme (GBM) is identified as WHO grade IV glioma and is the most common and aggressive malignant brain tumour, being highly invasive and not responsive to standard treatment regimen (surgical section, radio- and chemo-therapy). Therefore, the life expectancy after diagnosis is very poor, with a median survival of 15 months. We have previously shown that the Escherichia coli protein toxin CNF1 is remarkably effective as an anti-neoplastic agent in a mouse model of glioma, reducing the tumour volume, increasing the survival and maintaining the functional properties of peritumoural neurons. However, being unable to cross the blood-brain barrier (BBB), CNF1 requires to be directly injected into the brain, a very invasive administration route. Thus, to overcome this pitfall, we designed CNF1 variants characterised by the presence of N-terminal polycationic tags, known for their ability to address the Blood-Brains Barrier crossing when the chimera is intravenously injected. The variants were produced and we verified if their activity could overlap that of wild-type CNF1 in GMB cells. We investigated the signalling pathways engaged in the cell response to CNF1 variants with the aim of furnishing propaedeutic data to the subsequent studies in experimental animals. CNF1 may represent a novel avenue for glioma therapy particularly because, besides blocking tumour growth, also preserves the healthy surrounding tissue, maintaining its architecture and functionality. This renders CNF1 the most interesting candidate for the treatment of brain tumours, among other potentially effective bacterial toxins.

Botulinum Neurotoxins and Cancer

Shivam O Mittal M.D , Bahman Jabbari M.D, FAAN

 Abstract: Botulinum neurotoxins (BoNT) possess an analgesic effect through several mechanisms including inhibition of acetylcholine release from neuromuscular junction as well as inhibition of specific pain transmitters and mediators.   This review provides an updated information on the effect of local botulinum toxin injection on local pain caused by cancer, pain at the site of cancer surgery and radiation.  The data from literature suggests that local injection of botulinum toxins improves muscle spasms caused by cancerous mass lesions and alleviates the post-operative neuropathic pain at the site of surgery and radiation.  A limited literature that claims adding botulinum toxins to cell culture slows /halts the growth of certain cancer cells is also reviewed and discussed.

Key words: Botulinum toxin, botulinum neurotoxin, cancer, cancer cells, neuropathic pain, post-surgical pain, post-radiation pain

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