TY - JOUR
T1 - Syngeneic mouse models of oral cancer are effectively targetedbyanti-cd44-basedNIR-PIT
AU - Nagaya, Tadanobu
AU - Nakamura, Yuko
AU - Okuyama, Shuhei
AU - Ogata, Fusa
AU - Maruoka, Yasuhiro
AU - Choyke, Peter L.
AU - Allen, Clint
AU - Kobayashi, Hisataka
N1 - Funding Information:
This research was supported by the Intramural Research Program of the NIH, NCI, Center for Cancer Research (ZIA BC011513).
Publisher Copyright:
©2017 American Association for Cancer Research.
PY - 2017/12
Y1 - 2017/12
N2 - Oral cavity squamous cell carcinoma (OSCC) is considered one of the most aggressive subtypes of cancer. Anti-CD44 monoclonal antibodies (mAb) are a potential therapy against CD44 expressing OSCC; however, to date the therapeutic effects have been disappointing. Here, a new cancer treatment is described, near-infrared photoimmunotherapy (NIR-PIT), that uses anti-CD44 mAbs conjugated to the photoabsorber IR700DX. This conjugate is injected into mice harboring one of three CD44 expressing syngeneic murine oral cancer cell (MOC) lines, MOC1 (immunogenic), MOC2 mKate2 (moderately immunogenic), and MOC2-luc (poorly immunogenic). Binding of the anti-CD44-IR700 conjugate was shown to be specific and cell-specific cytotoxicity was observed after exposure of the cells to NIR light in vitro. The anti-CD44-IR700 conjugate, when assessed in vivo, demonstrated deposition within the tumor with a high tumor-To-background ratio. Tumor-bearing mice were separated into four cohorts: no treatment; 100 mg of anti-CD44-IR700 i.v. only; NIR light exposure only; and 100 mg of anti-CD44-IR700 i.v. with NIR light exposure. NIR-PIT therapy, compared with the other groups, significantly inhibited tumor growth and prolonged survival in all three cell model systems. In conclusion, these data reveal that anti-CD44 antibodies are suitable as mAb-photoabsorber conjugates for NIR-PIT in MOC cells. Implications: This study using syngeneic mouse models, which better model the disease in humans than conventional xenografts, suggests that NIR-PIT with anti-CD44-IR700 is a potential candidate for the treatment of OSCC.
AB - Oral cavity squamous cell carcinoma (OSCC) is considered one of the most aggressive subtypes of cancer. Anti-CD44 monoclonal antibodies (mAb) are a potential therapy against CD44 expressing OSCC; however, to date the therapeutic effects have been disappointing. Here, a new cancer treatment is described, near-infrared photoimmunotherapy (NIR-PIT), that uses anti-CD44 mAbs conjugated to the photoabsorber IR700DX. This conjugate is injected into mice harboring one of three CD44 expressing syngeneic murine oral cancer cell (MOC) lines, MOC1 (immunogenic), MOC2 mKate2 (moderately immunogenic), and MOC2-luc (poorly immunogenic). Binding of the anti-CD44-IR700 conjugate was shown to be specific and cell-specific cytotoxicity was observed after exposure of the cells to NIR light in vitro. The anti-CD44-IR700 conjugate, when assessed in vivo, demonstrated deposition within the tumor with a high tumor-To-background ratio. Tumor-bearing mice were separated into four cohorts: no treatment; 100 mg of anti-CD44-IR700 i.v. only; NIR light exposure only; and 100 mg of anti-CD44-IR700 i.v. with NIR light exposure. NIR-PIT therapy, compared with the other groups, significantly inhibited tumor growth and prolonged survival in all three cell model systems. In conclusion, these data reveal that anti-CD44 antibodies are suitable as mAb-photoabsorber conjugates for NIR-PIT in MOC cells. Implications: This study using syngeneic mouse models, which better model the disease in humans than conventional xenografts, suggests that NIR-PIT with anti-CD44-IR700 is a potential candidate for the treatment of OSCC.
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U2 - 10.1158/1541-7786.MCR-17-0333
DO - 10.1158/1541-7786.MCR-17-0333
M3 - Article
C2 - 28923838
AN - SCOPUS:85039845449
SN - 1541-7786
VL - 15
SP - 1667
EP - 1677
JO - Molecular Cancer Research
JF - Molecular Cancer Research
IS - 12
ER -