[Research] 2017/06/27

Bispecific antibody for targeting nanomedicines to cancer cells

A team led by Dr. Steve Roffler at the Institute of Biomedical Sciences (IBMS) in Academia Sinica and Dr. Tian-Lu Cheng at the Kaohsiung Medical University developed bispecific antibodies that can effectively target nanomedicines for safe and effective treatment of triple-negative breast cancer. The research was published in the journal Nature Communications on June 8th, 2017.


Nanomedicine is a promising new approach for cancer therapy in which medicines are encapsulated inside tiny nanometer-sized particles to reduce exposure to normal tissues and decrease side effects. At the same time, nanomedicines can target tumors by the enhanced permeability and retention effect in which nanometer-sized particles can pass through leaky blood vessels in tumors and accumulate near cancer cells. The bispecific antibodies developed by Roffler’s team are like a Venus fly trap. They can bind and remain on the surface of a cancer cell until a nanoparticle come close, at which time they trigger rapid uptake of the nanoparticle into the cancer cell.


First author Dr. Yu-Cheng Su said: “Typically, nanomedicines slowly release their drug payloads near the surface of cancer cells over time, which can limit treatment efficiency. By contrast, the bispecific antibodies we developed were able to both improve the uptake of PEGylated nanomedicines in tumors and increase the entry of nanomedicines into cancer cells, thus improving cancer treatment”


The bispecific antibodies, also called PEG engagers, bind to the epidermal growth factor receptor, which is highly expressed on many breast cancer tumor cells. The PEG engagers remains dormant on the surface of cancer cells until it contacts a nanoparticle. This triggers rapid internalization of the nanoparticle into the cancer cell, thereby enhancing the anti-cancer activity of the nanomedicine. Dr. Yu-Cheng Su remarked that the PEG engagers could enhance the anticancer activity of a clinically used nanomedicine called PEGylated-liposomal doxorubicin by up to 100-fold in cell culture experiments. The PEG engager also significantly enhanced the antitumor activity of PEGylated liposomal doxorubicin against human breast cancer in a mouse model.


Dr. Steve Roffler said, “We hope that our research can help patients suffering from cancer and other diseases. This simple and flexible strategy is a promising approach to enhance the delivery, safety and effectiveness of nanomedicines. It can be applied to other cancer types and other diseases by simply changing the targeting portion of the bispecific antibody.”


This work was supported by intramural funding from Academia Sinica and a grant from the Academia Sinica Research Program on Nanoscience and Nanotechnology. The full article entitled “Conditional internalization of PEGylated nanomedicines by PEG engagers for triple negative breast cancer therapy” can be found at the Nature Communications website at: https://www.nature.com/articles/ncomms15507


The complete list of authors is: Yu-Cheng Su, Pierre-Alain Burnouf, Kuo-Hsiang Chuang, Bing-Mae Chen, Tian-Lu Cheng & Steve R. Roffler