TY - JOUR
T1 - Overcoming the blood–brain barrier by Annexin A1-binding peptide to target brain tumours
AU - Nonaka, Motohiro
AU - Suzuki-Anekoji, Misa
AU - Nakayama, Jun
AU - Mabashi-Asazuma, Hideaki
AU - Jarvis, Donald L.
AU - Yeh, Jiunn Chern
AU - Yamasaki, Kazuhiko
AU - Akama, Tomoya O.
AU - Huang, Chun Teng
AU - Campos, Alexandre Rosa
AU - Nagaoka, Masato
AU - Sasai, Toshio
AU - Kimura-Takagi, Itsuko
AU - Suwa, Yoichi
AU - Yaegashi, Takashi
AU - Shibata, Toshiaki K.
AU - Sugihara, Kazuhiro
AU - Nishizawa-Harada, Chizuko
AU - Fukuda, Minoru
AU - Fukuda, Michiko N.
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/11/24
Y1 - 2020/11/24
N2 - 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.
AB - 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.
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U2 - 10.1038/s41416-020-01066-2
DO - 10.1038/s41416-020-01066-2
M3 - Article
C2 - 32921792
AN - SCOPUS:85090831245
SN - 0007-0920
VL - 123
SP - 1633
EP - 1643
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 11
ER -
