Allogeneic human neural stem cells for improved therapeutic delivery to peritoneal ovarian cancer

同种异体人类神经干细胞用于改善腹膜卵巢癌的治疗输送

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作者:Rachael Mooney, Wafa Abidi #, Jennifer Batalla-Covello #, Hoi Wa Ngai, Caitlyn Hyde, Diana Machado, Asma Abdul-Majid, Yanan Kang, Mohamed Hammad, Linda Flores, Greg Copeland, Thanh Dellinger, Ernest Han, Jacob Berlin, Karen S Aboody

Background

Immortalized, clonal HB1.F3.CD 21 human neural stem/progenitor cells (NSCs), loaded with therapeutic cargo prior to intraperitoneal (IP) injection, have been shown to improve the delivery and efficacy of therapeutic agents in pre-clinical models of stage III ovarian cancer. In previous studies, the distribution and efficacy of the NSC-delivered cargo has been examined; however, the fate of the NSCs has not yet been explored.

Conclusions

Their efficient tropism, combined with their promising clinical safety features and potential for cost-effective scale-up, positions this NSC line as a practical, off-the-shelf platform to improve the delivery of a myriad of peritoneal cancer therapeutics.

Methods

To monitor NSC tropism, we used an unconventional method of quantifying endocytosed gold nanorods to overcome the weaknesses of existing cell-tracking technologies.

Results

Here, we report efficient tumor tropism of HB1.F3.CD 21 NSCs, showing that they primarily distribute to the tumor stroma surrounding individual tumor foci within 3 h after injection, reaching up to 95% of IP metastases without localizing to healthy tissue. Furthermore, we demonstrate that these NSCs are non-tumorigenic and non-immunogenic within the peritoneal setting. Conclusions: Their efficient tropism, combined with their promising clinical safety features and potential for cost-effective scale-up, positions this NSC line as a practical, off-the-shelf platform to improve the delivery of a myriad of peritoneal cancer therapeutics.

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