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Anticancer Drugs ; 28(3): 263-270, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27861173

RESUMEN

Overexpression of epidermal growth factor receptor (EGFR) plays a significant role in the development and metastasis of many solid tumors. Strategies based on anti-EGFR immunotoxins have shown promising results in several studies, but immunogenicity of antibody and toxin moieties is a limitation of this type of therapeutics. In the present study, a novel humanized anti-EGFR immunotoxin (huscFv-PE25) was developed by genetic fusing of a humanized anti-EGFR single-chain variable fragment (huscFv) with a modified Pseudomonas aeruginosa exotoxin A (PE25KDEL). The reactivity and toxicity of this immunotoxin with tumor cells were assessed by dot-blot, enzyme-linked immunosorbent assay, and MTT procedures. Results of enzyme-linked immunosorbent assay and dot-blot assay indicated that the immunotoxin recognizes and efficiently binds to EGFR-overexpressing tumor cells. MTT assay showed a specific growth-inhibitory effect of huscFv-PE25 on EGFR-overexpressing A431 cells, without any inhibitory effect on EGFR-negative cells. In conclusion, the results of this study indicated that huscFv-PE25 can recognize and exert an inhibitory effect on EGFR-overexpressing cancer cells, despite its smaller size and lower immunogenicity. This may provide a basis for the development of novel clinical therapeutic agents against EGFR-overexpressing tumor cells.


Asunto(s)
ADP Ribosa Transferasas/farmacología , Toxinas Bacterianas/farmacología , Receptores ErbB/inmunología , Exotoxinas/farmacología , Inmunotoxinas/química , Inmunotoxinas/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Factores de Virulencia/farmacología , Células A549 , ADP Ribosa Transferasas/química , Animales , Toxinas Bacterianas/química , Células CHO , Línea Celular Tumoral , Cetuximab/farmacología , Cricetulus , Ensayo de Inmunoadsorción Enzimática , Receptores ErbB/biosíntesis , Exotoxinas/química , Región Variable de Inmunoglobulina/química , Región Variable de Inmunoglobulina/inmunología , Inmunotoxinas/inmunología , Inmunotoxinas/aislamiento & purificación , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/inmunología , Anticuerpos de Cadena Única/química , Anticuerpos de Cadena Única/inmunología , Neoplasias Cutáneas/enzimología , Neoplasias Cutáneas/inmunología , Factores de Virulencia/química , Exotoxina A de Pseudomonas aeruginosa
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