Bispecific Targeting of EGFR and Urokinase Receptor (uPAR) Using Ligand-Targeted Toxins in Solid Tumors
Ligand-targeted toxins (LTTs) are bioengineered molecules which are composed of a targeting component linked to a toxin that induces cell death once the LTT binds its target. Bispecific targeting allows for the simultaneous targeting of two receptors. In this review, we mostly focus on the epidermal...
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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/10/6/956 |
| _version_ | 1797564193201717248 |
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| author | Felix Oh Jaime F. Modiano Veronika Bachanova Daniel A. Vallera |
| author_facet | Felix Oh Jaime F. Modiano Veronika Bachanova Daniel A. Vallera |
| author_sort | Felix Oh |
| collection | DOAJ |
| description | Ligand-targeted toxins (LTTs) are bioengineered molecules which are composed of a targeting component linked to a toxin that induces cell death once the LTT binds its target. Bispecific targeting allows for the simultaneous targeting of two receptors. In this review, we mostly focus on the epidermal growth factor receptor (EGFR) as a target. We discuss the development and testing of a bispecific LTT targeting EGFR and urokinase-type plasminogen activator receptor (uPAR) as two attractive targets implicated in tumor growth and in the regulation of the tumor microvasculature in solid tumors. In vitro and mouse xenograft studies have shown that EGFR-targeted bispecific angiotoxin (eBAT) is effective against human solid tumors. Canine studies have shown that eBAT is both safe and effective against canine hemangiosarcoma, which is physiologically similar to human angiosarcoma. Finding the appropriate dosing strategy and sequencing of eBAT administration, in combination with other therapeutics, are among important factors for future directions. Together, the data indicate that eBAT targets cancer stem cells, it may have a role in inhibiting human tumor vasculature, and its bispecific conformation may have a role in reducing toxicity in comparative oncologic trials in dogs. |
| first_indexed | 2024-03-10T18:53:53Z |
| format | Article |
| id | doaj.art-008ae05eb6184091b2876890aa5dd1db |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T18:53:53Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-008ae05eb6184091b2876890aa5dd1db2023-11-20T04:54:54ZengMDPI AGBiomolecules2218-273X2020-06-0110695610.3390/biom10060956Bispecific Targeting of EGFR and Urokinase Receptor (uPAR) Using Ligand-Targeted Toxins in Solid TumorsFelix Oh0Jaime F. Modiano1Veronika Bachanova2Daniel A. Vallera3School of Medicine, Department of Radiation Oncology, University of Minnesota, Minneapolis, MN 55455 USAMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USAMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USASchool of Medicine, Department of Radiation Oncology, University of Minnesota, Minneapolis, MN 55455 USALigand-targeted toxins (LTTs) are bioengineered molecules which are composed of a targeting component linked to a toxin that induces cell death once the LTT binds its target. Bispecific targeting allows for the simultaneous targeting of two receptors. In this review, we mostly focus on the epidermal growth factor receptor (EGFR) as a target. We discuss the development and testing of a bispecific LTT targeting EGFR and urokinase-type plasminogen activator receptor (uPAR) as two attractive targets implicated in tumor growth and in the regulation of the tumor microvasculature in solid tumors. In vitro and mouse xenograft studies have shown that EGFR-targeted bispecific angiotoxin (eBAT) is effective against human solid tumors. Canine studies have shown that eBAT is both safe and effective against canine hemangiosarcoma, which is physiologically similar to human angiosarcoma. Finding the appropriate dosing strategy and sequencing of eBAT administration, in combination with other therapeutics, are among important factors for future directions. Together, the data indicate that eBAT targets cancer stem cells, it may have a role in inhibiting human tumor vasculature, and its bispecific conformation may have a role in reducing toxicity in comparative oncologic trials in dogs.https://www.mdpi.com/2218-273X/10/6/956EGFR (epidermal growth factor receptor)uPAR (urokinase-type plasminogen activator receptor)bispecificangiogenesisimmunotoxinLTT (ligand-targeted toxin) |
| spellingShingle | Felix Oh Jaime F. Modiano Veronika Bachanova Daniel A. Vallera Bispecific Targeting of EGFR and Urokinase Receptor (uPAR) Using Ligand-Targeted Toxins in Solid Tumors Biomolecules EGFR (epidermal growth factor receptor) uPAR (urokinase-type plasminogen activator receptor) bispecific angiogenesis immunotoxin LTT (ligand-targeted toxin) |
| title | Bispecific Targeting of EGFR and Urokinase Receptor (uPAR) Using Ligand-Targeted Toxins in Solid Tumors |
| title_full | Bispecific Targeting of EGFR and Urokinase Receptor (uPAR) Using Ligand-Targeted Toxins in Solid Tumors |
| title_fullStr | Bispecific Targeting of EGFR and Urokinase Receptor (uPAR) Using Ligand-Targeted Toxins in Solid Tumors |
| title_full_unstemmed | Bispecific Targeting of EGFR and Urokinase Receptor (uPAR) Using Ligand-Targeted Toxins in Solid Tumors |
| title_short | Bispecific Targeting of EGFR and Urokinase Receptor (uPAR) Using Ligand-Targeted Toxins in Solid Tumors |
| title_sort | bispecific targeting of egfr and urokinase receptor upar using ligand targeted toxins in solid tumors |
| topic | EGFR (epidermal growth factor receptor) uPAR (urokinase-type plasminogen activator receptor) bispecific angiogenesis immunotoxin LTT (ligand-targeted toxin) |
| url | https://www.mdpi.com/2218-273X/10/6/956 |
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