توسعه یک روش جدید ضد انژیوژنزیز بر پایه ژن درمانی برای درمان سرطان
A gene-based anti-angiogenesis therapy as a novel strategy for cancer treatment
نویسندگان: اصغر فلاح , حمیدرضا حیدری سورشجانی , بهزاد برادران , ام لیلا مولوی
کلمات کلیدی: Antibody gene therapy
Anti-angiogenesis
Cancer
Bevacizumab
Recombinant lentivirus gene delivery system
نشریه: 22959 , 117018 , 239 , 2019
| نویسنده ثبت کننده مقاله |
ام لیلا مولوی |
| مرحله جاری مقاله |
تایید نهایی |
| دانشکده/مرکز مربوطه |
دانشکده داروسازی |
| کد مقاله |
70106 |
| عنوان فارسی مقاله |
توسعه یک روش جدید ضد انژیوژنزیز بر پایه ژن درمانی برای درمان سرطان |
| عنوان لاتین مقاله |
A gene-based anti-angiogenesis therapy as a novel strategy for cancer treatment |
| ناشر |
6 |
| آیا مقاله از طرح تحقیقاتی و یا منتورشیپ استخراج شده است؟ |
بلی |
| عنوان نشریه (خارج از لیست فوق) |
|
| نوع مقاله |
Original Article |
| نحوه ایندکس شدن مقاله |
ایندکس شده سطح یک – ISI - Web of Science |
| آدرس لینک مقاله/ همایش در شبکه اینترنت |
|
| Angiogenesis-targeted therapy of cancer is considered a promising strategy for therapeutic management of
cancer progression. Over the last two decades, a few anti-angiogenesis monoclonal antibodies (mAbs) blocking
VEGF signaling have been developed and approved by the FDA. The most widely used anti-angiogenesis drug is
bevacizumab which binds VEGFA and prevents its interaction with VEGF receptor leading to suppression of
angiogenesis. Despite the remarkable success in development of angiogenesis inhibitory mAbs, their clinical
application is limited by the high-cost of mAbs-based regimen which includes multiple doses of mAbs due to
their short biological half-life. Antibody gene therapy is an alternative system of antibody production. In this
study, we have developed a gene-based anti-VEGF mAb system which is expected to produce a high concentration
of anti-VEGFA mAb upon a single administration in cancer patients. The full-length cDNA bevacizumab
light and heavy chains joint with T2A sequence were cloned in pCDH lentivirus vector. The lentiviral
particles expressing bevacizumab was produced in HEK-293T cells. Recombinant lentiviral particles containing
bevacizumab (rLV-bev) efficiently transduced HEK-293cells and produced functional bevacizumab mAb.
Bevacizumab expression in the transduced cell was assessed by qRT-PCR and western blot at both the mRNA and
protein level, respectively. The functionality of the recombinant bevacizumab was confirmed using the tube
formation assay in the co-culture system of endothelial cells and HT-29cells transduced with rLV-bev viral
particles. Our results show that rLV-bev gene therapy can be useful for angiogenesis-targeted therapy of cancer. |
| نام فایل |
تاریخ درج فایل |
اندازه فایل |
دانلود |
| Fallah Life sceince 2019.pdf | 1398/09/09 | 2904277 | دانلود |