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Book ChapterDOI

Application of Microbial Toxins for Cancer Therapy

TLDR
Continuous efforts are being made to improve the specificity and efficacy of immunotoxins, to reduce size effects of the drugs, reduce immunogenicity and to improve better pharmacokinetics for drugs delivery.
Abstract
The principle of selective targeting of immunotoxins lies on the basis that cancer cells usually have few or specific growth factors/receptors/antigens highly over expressed on their surface. Ligands corresponding to these molecules are conjugated to modified toxins (modified to loss its native function) isolated form variety of bacterial populations. Normal cells either do not express these molecules or express at relatively low number leading to no or minimal adverse effects. The basic mechanism of action of these immunotoxins depends on the toxins employed. In this regard continuous efforts are being made to (i) Identity molecules exclusively expressed in cancer cells, (ii) to improve the specificity and efficacy (iii) reduce size effects of the drugs, (iv) Reduce immunogenicity and (v) to improve better pharmacokinetics for drugs delivery.

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Citations
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Journal ArticleDOI

In Silico Analyses of Staphylococcal Enterotoxin B as a DNA Vaccine for Cancer Therapy

TL;DR: Assessment of the immunoreactivity of a SEB-coding DNA construct that serves as a DNA vaccine for breast cancer therapy revealed that apparently the construct could be efficiently expressed in mouse model, and could act as an amenable adjuvant in cancer immunotherapy.
References
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Journal ArticleDOI

Functional analysis of domains II, Ib, and III of Pseudomonas exotoxin.

TL;DR: Pseudomonas exotoxin is composed of three structural domains that are responsible for cell recognition, membrane translocation, and ADP-ribosylation, which creates a cell-specific cytotoxic agent, TGF alpha-PE40, which kills cells bearing epidermal growthfactor receptors.
Journal ArticleDOI

Phase I trial of a ligand fusion-protein (DAB389IL-2) in lymphomas expressing the receptor for interkeukin-2

TL;DR: DAB389IL-2 is well tolerated with an MTD of 27 micrograms/kg/day and showed antitumor effects in patients with IL-2 receptor expressing CTCL and NHL and additional trials in these diseases are warranted.
Journal ArticleDOI

ADP-ribosylation of elongation factor 2 by diphtheria toxin. Isolation and properties of the novel ribosyl-amino acid and its hydrolysis products.

TL;DR: The ribosyl-amino acid contains an amido function which is not involved in a glycosidic linkage and a net positive charge of 2 at acid pH and is concluded that the amino acid amide occurs in EF-2.
Journal ArticleDOI

Mutations in diphtheria toxin separate binding from entry and amplify immunotoxin selectivity

TL;DR: separation of the entry function from the binding function generates a uniquely potent and cell type-specific immunotoxin that retains full diphtheria toxin toxicity, yet is four to five orders of magnitude less toxic than the native toxin is to nontarget cells.
Journal ArticleDOI

Cloning and characterization of a cellular apoptosis susceptibility gene, the human homologue to the yeast chromosome segregation gene CSE1

TL;DR: The conservation of this gene indicates it has an important function in human cells consistent with the essential role of CSE1 in yeast, and appears to play an important role in both toxin and tumor necrosis factor-mediated cell death, as well as in cell proliferation.
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