این سایت در حال حاضر پشتیبانی نمی شود و امکان دارد داده های نشریات بروز نباشند
Iranian Journal of Immunology، جلد ۲۰، شماره ۳، صفحات ۳۰۳-۳۱۵
عنوان فارسی
چکیده فارسی مقاله
کلیدواژه‌های فارسی مقاله
عنوان انگلیسی Synthesized Anti-HER2 Trastuzumab-MCC-DM1 Conjugate: An Evaluation of Efficacy and Cytotoxicity
چکیده انگلیسی مقاله Background: Trastuzumab is a humanized monoclonal antibody that targets site-specifically human epidermal growth factor-2 receptor (HER2) cell surface antigen overexpressed in approximately 20% of human breast carcinomas. Despite its positive therapeutic outcomes, a large proportion of individuals are unresponsive to the treatment with trastuzumab or develop resistance to it.Objective: To evaluate a chemically synthesized trastuzumab-based antibody-drug conjugate (ADC) to improve the trastuzumab therapeutic index.Methods: The current study explored the physiochemical characteristics of the trastuzumab conjugated to a cytotoxic chemotherapy agent DM1 via Succinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) linker, created in our earlier study, using SDS-PAGE, UV/VIS, and RP-HPLC analyses. The antitumor effects of the ADCs were analyzed using MDA-MB-231 (HER2-negative) and SK-BR-3 (HER2-positive) cell lines utilizing in vitro cytotoxicity, viability, and binding assays. Three different formats of a HER2-targeting agent: trastuzumab, synthesized trastuzumab-MCC-DM1, and commercially available drug T-DM1 (Kadcyla®) were compared.Results: UV-VIS spectroscopic analysis showed that the trastuzumab-MCC-DM1 conjugates, on average, entailed 2.9 DM1 payloads per trastuzumab. A free drug level of 2.5% was determined by RP-HPLC. The conjugate appeared as two bands on a reducing SDS-PAGE gel. MTT viability assay showed that conjugating trastuzumab with DM1 significantly improved the antiproliferative effects of this antibody in vitro. Importantly, the evaluations using LDH release and cell apoptosis assays confirmed that trastuzumab maintains its ability to induce cell death response while conjugating with the DM1. The binding efficiency of trastuzumab-MCC-DM1 was comparable to that of the naked trastuzumab.Conclusion: Trastuzumab-MCC-DM1 was found effective against HER2+ tumors. The potency of this synthesized conjugate brings it closer to the commercially available T-DM1.
کلیدواژه‌های انگلیسی مقاله Breast neoplasms, Immunoconjugates, Therapeutic Index, Trastuzumab
نویسندگان مقاله Soodabeh Shafiee |
Department of Recombinant Proteins, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.

Roya Mirzaei |
Department of Recombinant Proteins, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.

Malihe Salehi |
Department of Recombinant Proteins, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.

Neda Jalili |
Department of Recombinant Proteins, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.

Amir Taheri |
Department of Recombinant Proteins, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.

Leila Farahmand |
Department of Recombinant Proteins, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.

نشانی اینترنتی https://iji.sums.ac.ir/article_49411_07f4888549d6cfb0b706534f398c5e5b.pdf
فایل مقاله فایلی برای مقاله ذخیره نشده است
کد مقاله (doi)
زبان مقاله منتشر شده en
موضوعات مقاله منتشر شده
نوع مقاله منتشر شده
برگشت به: صفحه اول پایگاه   |   نسخه مرتبط   |   نشریه مرتبط   |   فهرست نشریات