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2015 ; 10
(8
): e0136829
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Near Infrared Photoimmunotherapy Targeting EGFR Positive Triple Negative Breast
Cancer: Optimizing the Conjugate-Light Regimen
#MMPMID26313651
Nagaya T
; Sato K
; Harada T
; Nakamura Y
; Choyke PL
; Kobayashi H
PLoS One
2015[]; 10
(8
): e0136829
PMID26313651
show ga
AIM: Triple-negative breast cancer (TNBC) is considered one of the most
aggressive subtypes of breast cancer. Near infrared photoimmunotherapy (NIR-PIT)
is a cancer treatment that employs an antibody-photosensitizer conjugate (APC)
followed by exposure of NIR light for activating selective cytotoxicity on
targeted cancer cells and may have application to TNBC. In order to minimize the
dose of APC while maximizing the therapeutic effects, dosing of the APC and NIR
light need to be optimized. In this study, we investigate in vitro and in vivo
efficacy of cetuximab (cet)-IR700 NIR-PIT on two breast cancer models MDAMB231
(TNBC, EGFR moderate) and MDAMB468 (TNBC, EGFR high) cell lines, and demonstrate
a method to optimize the dosing APC and NIR light. METHOD: After validating in
vitro cell-specific cytotoxicity, NIR-PIT therapeutic effects were investigated
in mouse models using cell lines derived from TNBC tumors. Tumor-bearing mice
were separated into 4 groups for the following treatments: (1) no treatment
(control); (2) 300 ?g of cet-IR700 i.v., (APC i.v. only); (3) NIR light exposure
only, NIR light was administered at 50 J/cm2 on day 1 and 100 J/cm2 on day 2 (NIR
light only); (4) 300 ?g of cet-IR700 i.v., NIR light was administered at 50 J/cm2
on day 1 after injection and 100 J/cm2 of light on day 2 after injection (one
shot NIR-PIT). To compare different treatment regimens with a fixed dose of APC,
we added the following treatments (5) 100 ?g of cet-IR700 i.v., NIR light
administered at 50 J/cm2 on day 1 and 50 ?g of cet-IR700 i.v. immediately after
NIR-PIT, then NIR light was administered at 100 J/cm2 on day 2, which were
performed two times every week ("two split" NIR-PIT) and (6) 100 ?g of cet-IR700
i.v., NIR light was administered at 50 J/cm2 on day 1 and 100 J/cm2 on day 2,
which were performed three times per week ("three split" NIR-PIT). RESULT: Both
specific binding and NIR-PIT effects were greater with MDAMB468 than MDAMB231
cells in vitro. Tumor accumulation of cet-IR700 in MDAMB468 tumors was
significantly higher (p < 0.05) than in MDAMB231 tumors in vivo. Tumor growth and
survival of MDAMB231 tumor bearing mice was significantly lower in the NIR-PIT
treatment group (p < 0.05). In MDAMB468 bearing mice, tumor growth and survival
was significantly improved in the NIR-PIT treatment groups in all treatment
regimens (one shot NIR-PIT; p < 0.05, "two split" NIR-PIT; p < 0.01, "three
split" NIR-PIT; p < 0.001) compared with control groups. CONCLUSION: NIR-PIT for
TNBC was effective regardless of expression of EGFR, however, greater cell
killing was shown with higher EGFR expression tumor in vitro. In all treatment
regimens, NIR-PIT suppressed tumor growth, resulting in significantly prolonged
survival that further improved by splitting the APC dose and using repeated light
exposures.