چاپ صفحه |  صفحه نخست سامانه |  نویسندگان |  اطلاعات تفضیلی |  دانلود مقاله | علوم پزشکی کرمانشاه |
| نویسنده | نفر چندم مقاله |
|---|---|
| بهمن اکبری | اول |
| عنوان | متن |
|---|---|
| کلمات کلیدی | Cancer therapy, Targeted therapy, Immunotoxin |
| چکیده | Abstract Despite promising initial responses, most advanced solid tumors develop resistance to conventional treatments. Development of new cancer therapies is based on the design of drugs that targets specifically to cancer cells while have minimal adverse effects on normal tissues. Targeted therapy is based on application of antibodies, ligands and peptides specific to molecules on cancer cells. Immunotoxins (ITs) are new generation targeted therapies in which targeting molecules are conjugated to toxins, enzymes and other toxic agents. Denileukin Diftitox, has been approved as a first IT for cutaneous T cell lymphoma in 1999. Here we describe the design, construction, bacterial expression and in-vitro characterization of an anti-EGFR immunotoxin. Materials and methods: In the design of this immunotoxin, the sequence of Pseudomonas exotoxin A was modified. Also a humanized anti-EGFR single- chain antibody was designed based on cetuximab monoclonal antibody and conjugated to modified toxin. The result of IT was affinity purified after expression in E. coli. The reactivity and cell growth inhibition potential of IT was assessed by ELISA and MTT assay, respectively. Result: Expression analysis showed that the IT was produced in a high concentration in E. coli. Investigation of reactivity and cytotoxicity of the purified IT on EGFR over expressing tumoral cells showed that this IT was able to detect, react and kill the target cells. Conclusion: The result of our study indicates that developed IT could be a good candidate in the treatment of EGFR-overexpressing tumors. |
| متن مقاله | Abstract Despite promising initial responses, most advanced solid tumors develop resistance to conventional treatments. Development of new cancer therapies is based on the design of drugs that targets specifically to cancer cells while have minimal adverse effects on normal tissues. Targeted therapy is based on application of antibodies, ligands and peptides specific to molecules on cancer cells. Immunotoxins (ITs) are new generation targeted therapies in which targeting molecules are conjugated to toxins, enzymes and other toxic agents. Denileukin Diftitox, has been approved as a first IT for cutaneous T cell lymphoma in 1999. Here we describe the design, construction, bacterial expression and in-vitro characterization of an anti-EGFR immunotoxin. Materials and methods: In the design of this immunotoxin, the sequence of Pseudomonas exotoxin A was modified. Also a humanized anti-EGFR single- chain antibody was designed based on cetuximab monoclonal antibody and conjugated to modified toxin. The result of IT was affinity purified after expression in E. coli. The reactivity and cell growth inhibition potential of IT was assessed by ELISA and MTT assay, respectively. Result: Expression analysis showed that the IT was produced in a high concentration in E. coli. Investigation of reactivity and cytotoxicity of the purified IT on EGFR over expressing tumoral cells showed that this IT was able to detect, react and kill the target cells. Conclusion: The result of our study indicates that developed IT could be a good candidate in the treatment of EGFR-overexpressing tumors. |
| نتیجه مقاله | Result: Expression analysis showed that the IT was produced in a high concentration in E. coli. Investigation of reactivity and cytotoxicity of the purified IT on EGFR over expressing tumoral cells showed that this IT was able to detect, react and kill the target cells. Conclusion: The result of our study indicates that developed IT could be a good candidate in the treatment of EGFR-overexpressing tumors. |
| نام فایل | تاریخ درج فایل | اندازه فایل | دانلود |
|---|---|---|---|
| img027.jpg | 1397/03/21 | 370329 | دانلود |
| article.pdf | 1397/03/21 | 9129 | دانلود |
| img029.jpg | 1397/03/21 | 334767 | دانلود |
| abstract book.pdf | 1397/03/21 | 4627281 | دانلود |
