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ABSTRACT: Background
Annexin A1 is expressed specifically on the tumour vasculature surface. Intravenously injected IF7 targets tumour vasculature via annexin A1. We tested the hypothesis that IF7 overcomes the blood-brain barrier and that the intravenously injected IF7C(RR)-SN38 eradicates brain tumours in the mouse.Methods
(1) A dual-tumour model was generated by inoculating luciferase-expressing melanoma B16 cell line, B16-Luc, into the brain and under the skin of syngeneic C57BL/6 mice. IF7C(RR)-SN38 was injected intravenously daily at 7.0 μmoles/kg and growth of tumours was assessed by chemiluminescence using an IVIS imager. A similar dual-tumour model was generated with the C6-Luc line in immunocompromised SCID mice. (2) IF7C(RR)-SN38 formulated with 10% Solutol HS15 was injected intravenously daily at 2.5 μmoles/kg into two brain tumour mouse models: B16-Luc cells in C57BL/6 mice, and C6-Luc cells in nude mice.Results
(1) Daily IF7C(RR)-SN38 injection suppressed tumour growth regardless of cell lines or mouse strains. (2) Daily injection of Solutol-formulated IF7C(RR)-SN38 led into complete disappearance of B16-Luc brain tumour in C57BL/6 mice, whereas this did not occur in C6-Luc in nude mice.Conclusions
IF7C(RR)-SN38 crosses the blood-brain barrier and suppresses growth of brain tumours in mouse models. Solutol HS15-formulated IF7C(RR)-SN38 may have promoted an antitumour immune response.
SUBMITTER: Nonaka M
PROVIDER: S-EPMC7686308 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
Nonaka Motohiro M Suzuki-Anekoji Misa M Nakayama Jun J Mabashi-Asazuma Hideaki H Jarvis Donald L DL Yeh Jiunn-Chern JC Yamasaki Kazuhiko K Akama Tomoya O TO Huang Chun-Teng CT Campos Alexandre Rosa AR Nagaoka Masato M Sasai Toshio T Kimura-Takagi Itsuko I Suwa Yoichi Y Yaegashi Takashi T Shibata Toshiaki K TK Sugihara Kazuhiro K Nishizawa-Harada Chizuko C Fukuda Minoru M Fukuda Michiko N MN
British journal of cancer 20200914 11
<h4>Background</h4>Annexin A1 is expressed specifically on the tumour vasculature surface. Intravenously injected IF7 targets tumour vasculature via annexin A1. We tested the hypothesis that IF7 overcomes the blood-brain barrier and that the intravenously injected IF7C(RR)-SN38 eradicates brain tumours in the mouse.<h4>Methods</h4>(1) A dual-tumour model was generated by inoculating luciferase-expressing melanoma B16 cell line, B16-Luc, into the brain and under the skin of syngeneic C57BL/6 mice ...[more]