Wafa Abidi1, Jennifer Batalla-Covello2,3, Rachael Mooney4, Hoi Wa Ngai2, Caitlyn Hyde2, Diana Machado2, Asma Abdul-Majid2, Yanan Kang3,1, Mohamed Hammad2, Linda Flores2, Greg Copeland1, Thanh Dellinger5, Ernest Han5, Jacob Berlin1, Karen S Aboody2. 1. Department of Molecular Medicine, Beckman Research Institute at City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA. 2. City of Hope Familian Sciences 1014A, Department of Developmental and Stem Cell Biology, Beckman Research Institute at City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA. 3. Irell & Manella Graduate School of Biological Sciences, Beckman Research Institute at City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA. 4. City of Hope Familian Sciences 1014A, Department of Developmental and Stem Cell Biology, Beckman Research Institute at City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA. rmooney@coh.org. 5. Division of Gynecologic Surgery, Beckman Research Institute at City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA.
Abstract
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. 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.
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. 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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