Cargando…
Plant-Derived Type I Ribosome Inactivating Protein-Based Targeted Toxins: A Review of the Clinical Experience
Targeted toxins (TT) for cancer treatment are a class of hybrid biologic comprised of a targeting domain coupled chemically or genetically to a proteinaceous toxin payload. The targeting domain of the TT recognises and binds to a defined target molecule on the cancer cell surface, thereby delivering...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9412999/ https://www.ncbi.nlm.nih.gov/pubmed/36006226 http://dx.doi.org/10.3390/toxins14080563 |
_version_ | 1784775630893613056 |
---|---|
author | Flavell, David J. Flavell, Sopsamorn U. |
author_facet | Flavell, David J. Flavell, Sopsamorn U. |
author_sort | Flavell, David J. |
collection | PubMed |
description | Targeted toxins (TT) for cancer treatment are a class of hybrid biologic comprised of a targeting domain coupled chemically or genetically to a proteinaceous toxin payload. The targeting domain of the TT recognises and binds to a defined target molecule on the cancer cell surface, thereby delivering the toxin that is then required to internalise to an appropriate intracellular compartment in order to kill the target cancer cell. Toxins from several different sources have been investigated over the years, and the two TTs that have so far been licensed for clinical use in humans; both utilise bacterial toxins. Relatively few clinical studies have, however, been undertaken with TTs that utilise single-chain type I ribosome inactivating proteins (RIPs). This paper reviews the clinical experience that has so far been obtained for a range of TTs based on five different type I RIPs and concludes that the majority studied in early phase trials show significant clinical activity that justifies further clinical investigation. A range of practical issues relating to the further clinical development of TT’s are also covered briefly together with some suggested solutions to outstanding problems. |
format | Online Article Text |
id | pubmed-9412999 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94129992022-08-27 Plant-Derived Type I Ribosome Inactivating Protein-Based Targeted Toxins: A Review of the Clinical Experience Flavell, David J. Flavell, Sopsamorn U. Toxins (Basel) Review Targeted toxins (TT) for cancer treatment are a class of hybrid biologic comprised of a targeting domain coupled chemically or genetically to a proteinaceous toxin payload. The targeting domain of the TT recognises and binds to a defined target molecule on the cancer cell surface, thereby delivering the toxin that is then required to internalise to an appropriate intracellular compartment in order to kill the target cancer cell. Toxins from several different sources have been investigated over the years, and the two TTs that have so far been licensed for clinical use in humans; both utilise bacterial toxins. Relatively few clinical studies have, however, been undertaken with TTs that utilise single-chain type I ribosome inactivating proteins (RIPs). This paper reviews the clinical experience that has so far been obtained for a range of TTs based on five different type I RIPs and concludes that the majority studied in early phase trials show significant clinical activity that justifies further clinical investigation. A range of practical issues relating to the further clinical development of TT’s are also covered briefly together with some suggested solutions to outstanding problems. MDPI 2022-08-18 /pmc/articles/PMC9412999/ /pubmed/36006226 http://dx.doi.org/10.3390/toxins14080563 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Flavell, David J. Flavell, Sopsamorn U. Plant-Derived Type I Ribosome Inactivating Protein-Based Targeted Toxins: A Review of the Clinical Experience |
title | Plant-Derived Type I Ribosome Inactivating Protein-Based Targeted Toxins: A Review of the Clinical Experience |
title_full | Plant-Derived Type I Ribosome Inactivating Protein-Based Targeted Toxins: A Review of the Clinical Experience |
title_fullStr | Plant-Derived Type I Ribosome Inactivating Protein-Based Targeted Toxins: A Review of the Clinical Experience |
title_full_unstemmed | Plant-Derived Type I Ribosome Inactivating Protein-Based Targeted Toxins: A Review of the Clinical Experience |
title_short | Plant-Derived Type I Ribosome Inactivating Protein-Based Targeted Toxins: A Review of the Clinical Experience |
title_sort | plant-derived type i ribosome inactivating protein-based targeted toxins: a review of the clinical experience |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9412999/ https://www.ncbi.nlm.nih.gov/pubmed/36006226 http://dx.doi.org/10.3390/toxins14080563 |
work_keys_str_mv | AT flavelldavidj plantderivedtypeiribosomeinactivatingproteinbasedtargetedtoxinsareviewoftheclinicalexperience AT flavellsopsamornu plantderivedtypeiribosomeinactivatingproteinbasedtargetedtoxinsareviewoftheclinicalexperience |