RETRACTED ARTICLE: Targeted suicide gene therapy for glioma using human embryonic stem cell-derived neural stem cells genetically modified by baculoviral vectors

Abstract

Tumor-tropic neural stem cells (NSCs) can be used in the Trojan horse approach as cellular vehicles for targeted delivery of therapeutic agents to distant tumor sites. To realize this cancer therapy potential, it is important to have a renewable source to generate large quantities of uniform human NSCs. Here, we reported that NSCs derived from HES1 human embryonic stem cell line were capable of migrating into intracranial glioma xenografts after systemic injection or after intracranial injection at a site distant from the tumor. To test whether the HES1-derived NSCs can be used for cancer gene therapy, we used a baculoviral vector to introduce the herpes simplex virus thymidine kinase suicide gene into the cells and demonstrated that baculovirusmediated transgene expression may last for at least 3 weeks in NSCs. After being injected into the cerebral hemisphere opposite the tumor site and in the presence of ganciclovir, NSCs expressing the suicide gene were able to inhibit the growth of human glioma xenografts and prolong survival of tumor-bearing mice. Our findings suggest that human embryonic stem cells could potentially serve as a clinically viable source for production of cellular vehicles suitable for targeted anticancer gene therapy.

Adaptive Immune Responses Elicited by Baculovirus and Impacts on Subsequent Transgene Expression In Vivo

“…These attributes have prompted the development of BV vectors for in vitro and in vivo gene delivery (3), RNA interference (4), cell-based assay development (5), production of viral vectors (6) and recombinant proteins (7), as well as cartilage and bone tissue engineering (8). Beyond these applications, BV is also used as an expression vector for the treatment of various cancers, including hepatoma (9), melanoma (10), colon cancer (11), brain cancer (12)(13)(14)(15)(16), prostate cancer (17,18), and ovarian cancer (17). In addition, BV has been explosively developed as a vaccine expression/display vector against a variety of pathogens, including avian influenza virus (AIV) (19)(20)(21)(22), avian reovirus (23), pseudorabies virus (24), enterovirus 71 (25), Plasmodium berghei (26), and many others (for a review, see reference 1).…”

Development of Anti-Cancer Stem Cells as Theranostic Agents in the Treatment of Different Cancer Types: An Update

“…Carboxylesterase (CE) enzyme has a role in the conversion of pro-drug irinotecan to topoisomerase inhibitor SN-38. In the adaptation of MSCs and NSCs, CD-5-FC system has been used and this system is good for the practice in mouse models for the treatment of brain tumors, for example glioblastoma and medulloblastoma, that consequent on the failure of tumor mass and continued existence [173][174][175][176][177]. The HSV-Tk system which depends upon the development of gap junctions in between the SC and target cells found nearby for competent results that have shown efficiency in various various animal models of cancer, which includes glioblastoma, breast cancer and prostate [178][179][180].…”

Frontiers in Suicide Gene Therapy of Cancer

“…HSV-TK is effectively used in cancer suicide gene therapy by expression in targeted cells to exert intracellular effects outlined above [15][16][17][18][19][22][23][24]. Alternatively, TK is also secreted into the extracellular fluids by genetically engineered cells [135][136][137][138][139][140][141][142][143][144][145][146][147][148]. Thereafter, it is internalized by surrounding cancer cells to cause their death.…”

“…The stem cells are being tested for their potential for carrying the suicidal genes also into variety of other tumors [135][136][137][138][139][140][141][142][143][144][145][146][147][148].…”