Mechanisms of Resistance to Immunotoxins Containing <i>Pseudomonas</i> Exotoxin A in Cancer Therapy
Immunotoxins are a class of targeted cancer therapeutics in which a toxin such as <i>Pseudomonas</i> exotoxin A (PE) is linked to an antibody or cytokine to direct the toxin to a target on cancer cells. While a variety of PE-based immunotoxins have been developed and a few have demonstra...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/7/979 |
| _version_ | 1797563738204667904 |
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| author | Michael Dieffenbach Ira Pastan |
| author_facet | Michael Dieffenbach Ira Pastan |
| author_sort | Michael Dieffenbach |
| collection | DOAJ |
| description | Immunotoxins are a class of targeted cancer therapeutics in which a toxin such as <i>Pseudomonas</i> exotoxin A (PE) is linked to an antibody or cytokine to direct the toxin to a target on cancer cells. While a variety of PE-based immunotoxins have been developed and a few have demonstrated promising clinical and preclinical results, cancer cells frequently have or develop resistance to these immunotoxins. This review presents our current understanding of the mechanism of action of PE-based immunotoxins and discusses cellular mechanisms of resistance that interfere with various steps of the pathway. These steps include binding of the immunotoxin to the target antigen, internalization, intracellular processing and trafficking to reach the cytosol, inhibition of protein synthesis through ADP-ribosylation of elongation factor 2 (EF2), and induction of apoptosis. Combination therapies that increase immunotoxin action and overcome specific mechanisms of resistance are also reviewed. |
| first_indexed | 2024-03-10T18:46:36Z |
| format | Article |
| id | doaj.art-8c9d9c0ff0604b69a3e566c12e21ed3d |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T18:46:36Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-8c9d9c0ff0604b69a3e566c12e21ed3d2023-11-20T05:27:13ZengMDPI AGBiomolecules2218-273X2020-06-0110797910.3390/biom10070979Mechanisms of Resistance to Immunotoxins Containing <i>Pseudomonas</i> Exotoxin A in Cancer TherapyMichael Dieffenbach0Ira Pastan1Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4264, USALaboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4264, USAImmunotoxins are a class of targeted cancer therapeutics in which a toxin such as <i>Pseudomonas</i> exotoxin A (PE) is linked to an antibody or cytokine to direct the toxin to a target on cancer cells. While a variety of PE-based immunotoxins have been developed and a few have demonstrated promising clinical and preclinical results, cancer cells frequently have or develop resistance to these immunotoxins. This review presents our current understanding of the mechanism of action of PE-based immunotoxins and discusses cellular mechanisms of resistance that interfere with various steps of the pathway. These steps include binding of the immunotoxin to the target antigen, internalization, intracellular processing and trafficking to reach the cytosol, inhibition of protein synthesis through ADP-ribosylation of elongation factor 2 (EF2), and induction of apoptosis. Combination therapies that increase immunotoxin action and overcome specific mechanisms of resistance are also reviewed.https://www.mdpi.com/2218-273X/10/7/979immunotoxin<i>Pseudomonas</i> exotoxin Aimmunotoxin resistancecombination therapy |
| spellingShingle | Michael Dieffenbach Ira Pastan Mechanisms of Resistance to Immunotoxins Containing <i>Pseudomonas</i> Exotoxin A in Cancer Therapy Biomolecules immunotoxin <i>Pseudomonas</i> exotoxin A immunotoxin resistance combination therapy |
| title | Mechanisms of Resistance to Immunotoxins Containing <i>Pseudomonas</i> Exotoxin A in Cancer Therapy |
| title_full | Mechanisms of Resistance to Immunotoxins Containing <i>Pseudomonas</i> Exotoxin A in Cancer Therapy |
| title_fullStr | Mechanisms of Resistance to Immunotoxins Containing <i>Pseudomonas</i> Exotoxin A in Cancer Therapy |
| title_full_unstemmed | Mechanisms of Resistance to Immunotoxins Containing <i>Pseudomonas</i> Exotoxin A in Cancer Therapy |
| title_short | Mechanisms of Resistance to Immunotoxins Containing <i>Pseudomonas</i> Exotoxin A in Cancer Therapy |
| title_sort | mechanisms of resistance to immunotoxins containing i pseudomonas i exotoxin a in cancer therapy |
| topic | immunotoxin <i>Pseudomonas</i> exotoxin A immunotoxin resistance combination therapy |
| url | https://www.mdpi.com/2218-273X/10/7/979 |
| work_keys_str_mv | AT michaeldieffenbach mechanismsofresistancetoimmunotoxinscontainingipseudomonasiexotoxinaincancertherapy AT irapastan mechanismsofresistancetoimmunotoxinscontainingipseudomonasiexotoxinaincancertherapy |