Targeting Breast Cancers with Neural Stem Cells

Singapore scientists, in particular researchers at the Institute of Bioengineering and Nanotechnology (IBN) showed that engineered neural stem cells can target and kill breast cancers.

In this study, workers in the laboratory of Shu Wang used mouse induced pluripotent stem cells (iPSCs) and differentiated them into neural stem cells (NSCs). They then engineered the NSCs to express a viral gene called thymidine kinase. Thymidine kinase comes from Herpes viruses, and this is particular gene that is not found in human cells. Therefore it is a target for anti-herpes virus drugs. By using an insect virus called “baculovirus,” Wang and his colleagues introduced thymidine kinase into NSCs. The use of baculovirus makes the NSCs safer for clinical use, since, being an insect virus, it does not grow in human cells, but can introduce genes into them.

By placing the herpes thymidine kinase gene into NSCs, it makes from susceptible to antiherpes drugs. For example, ganciclovir (Cytovene), is phosphorylated by thymidine kinase, and this molecule is quite toxic to cells. Contact between the engineered NSCs and cancer cells, would cause transfer of the toxic molecule to the cancer cells, which would kill cancer cells too. However, this begs the question: Can NSCs home to the tumor and target it?

In order to test the ability of NSCs to target and treat breast cancers, Wu’s group injected NSCs loaded with the suicide gene mice afflicted with breast tumors. Then they treated the mice with ganciclovir. Dual-colored whole body imaging was used to track the distribution and migration of the engineered NSCs.

Imaging showed that the NSCs homed in on the breast tumors in the mice, and accumulated in various organs that were infiltrated by the cancer cells. The survival of the tumor-bearing mice was prolonged from 34 days to 39 days. These data demonstrate that iPS-derived NSCs are able to effectively seek out and inhibit tumor growth and proliferation.

According to Dr Shu Wang, “We have demonstrated that tumor-targeting neural stem cells may be derived from human iPS cells, and that these cells may be used in combination with a therapeutic gene to cripple tumor growth. This is a significant finding for stem cell-based cancer therapy, and we will continue to improve and optimize our neural stem cell system by preventing any unwanted activation of the therapeutic gene in non-tumor regions and minimizing possible side effects.”

Professor Jackie. Y. Ying, IBN Executive Director, said, “IBN’s expertise in generating human stem cells from iPS cells and our novel use of insect virus carriers for gene delivery have paved the way for the development of innovative stem cell-based therapies. With their two-pronged attack on tumors using genetically engineered neural stem cells, our researchers have discovered a promising alternative to conventional cancer treatment.