Bispecific antibody complex pre-targeted delivery of polymer-drug conjugates for cancer therapy

Drug Delivery and Translational Research
Keyur S GadaBan-An Khaw

Abstract

The pretargeting approach using bispecific affibody-antibody complex (BAAC) and targeting of chemotherapeutic drug loaded polymers have been used in breast cancer cell cultures to demonstrate targeted chemotherapy and reduce toxicity to non-pretargeted cancer and cardiac cells. HER2/neu-positive BT-474 and -negative BT-20 human mammary carcinoma cell lines were pretargeted with BAAC and targeted with multi-doxorubicin (Dox) loaded polyglutamic acid (PGA) site specifically modified with diethylene triamine pentaacetic acid (DTPA) (D-Dox-PGA) at the N-terminal of PGA. Toxicity to embryonic cardiocytes and human mammary carcinoma cells were assessed. BAAC was prepared by covalent conjugation of anti-HER2/neu affibody and anti-DTPA Fab via the thioether linkage. N-terminal DTPA modified polyglutamic acid was conjugated with doxorubicin via the amide bonds. Reduction in cardiotoxicity and IC50 of D-Dox-PGA and free Dox were determined in embryonic cardiocyte H9C2 cultures. Enhanced targeted tumor toxicity was demonstrated in BT-474 human mammary carcinoma cell line pretargeting with BAAC followed by targeting with D-Dox-PGA and compared to D-Dox-PGA alone with no pretargeting or free Dox. No enhanced targeted tumor toxicity was obse...Continue Reading

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Citations

Sep 27, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Qi YangSamuel K Lai
Oct 19, 2016·Macromolecular Bioscience·Oleksandr ZagorodkoMaría J Vicent
Feb 3, 2018·Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology·Rajiv PanwarBan An Khaw
Nov 25, 2014·Expert Opinion on Orphan Drugs·Shunji TomatsuTadao Orii
Jul 21, 2014·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Jun WangCheng Zhi Huang

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