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• W4313243969 abstract "The epidermal growth factor receptor (EGFR) remains one of the best molecules for developing targeted therapy for multiple human malignancies, including head and neck squamous cell carcinoma (HNSCC). Small molecule inhibitors or antibodies targeting EGFR have been extensively developed in recent decades. Immunotoxin (IT)‑based therapy, which combines cell surface binding ligands or antibodies with a peptide toxin, represents another cancer treatment option. A total of 3 diphtheria toxin (DT)‑based fusion toxins that target human EGFR‑monovalent EGFR IT (mono‑EGF‑IT), bivalent EGFR IT (bi‑EGF‑IT), and a bispecific IT targeting both EGFR and interleukin‑2 receptor (bis‑EGF/IL2‑IT) were recently generated by the authors. Improved efficacy and reduced toxicity of bi‑EGF‑IT compared with mono‑EGF‑IT in immunocompromised HNSCC mouse models was reported. In the present study, bis‑EGF/IL2‑IT were generated using a unique DT‑resistant yeast expression system and evaluated the <em>in vitro</em> and <em>in vivo</em> efficacy and toxicity of the 3 EGF‑ITs in immunocompetent mice. The results demonstrated that while the three EGF‑ITs had different efficacies <em>in vitro</em> and <em>in vivo</em> against HNSCC, bi‑EGF‑IT and bis‑EGF/IL2‑IT had significantly improved <em>in vivo</em> efficacy and remarkably less off‑target toxicity compared with mono‑EGF‑IT. In addition, bis‑EGF/IL2‑IT was superior to bi‑EGF‑IT in reducing tumor size and prolonging survival in the metastatic model. These data suggested that targeting either the tumor immune microenvironment or enhancing the binding affinity could improve the efficacy of IT‑based therapy. Bi‑EGF‑IT and bis‑EGF/IL2‑IT represent improved candidates for IT‑based therapy for future clinical development." @default.
• W4313243969 created "2023-01-06" @default.
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• W4313243969 date "2022-12-27" @default.
• W4313243969 modified "2023-10-14" @default.
• W4313243969 title "EGF‑IL2 bispecific and bivalent EGF fusion toxin efficacy against syngeneic head and neck cancer mouse models" @default.
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• W4313243969 doi "https://doi.org/10.3892/or.2022.8474" @default.
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