Molecular targeted photoimmunotherapy for HER2-positive human gastric cancer in combination with chemotherapy results in improved treatment outcomes through different cytotoxic mechanisms

BMC Cancer
Kimihiro ItoHisao Tajiri

Abstract

Photoimmunotherapy (PIT) is a novel type of molecular optical imaging-guided cancer phototherapy based on a monoclonal antibody conjugated to a photosensitizer, IR700, in combination with near-infrared (NIR) light. PIT rapidly causes target-specific cell death by inducing cell membrane damages and appears to be highly effective; however, we have previously demonstrated that tumor recurrences were eventually seen in PIT-treated mice, likely owing to inhomogeneous mAb-IR700 conjugate distribution in the tumor, thus limiting the effectiveness of PIT as a monotherapy. Here, we examined the effects of human epidermal growth factor-2 (HER2)-targeted PIT in combination with 5-fluorouracil (5-FU) compared to PIT alone for HER2-expressing human gastric cancer cells. NCI-N87 cells, HER2-positive human gastric cancer cells, were used for the experiments. Trastuzumab, a monoclonal antibody directed against HER2, was conjugated to IR700. To assess the short-term cytotoxicity and examine the apoptotic effects upon addition of 5-FU in vitro, we performed LIVE/DEAD and caspase-3 activity assays. Additionally, to explore the effects on long-term growth inhibition, trypan blue dye exclusion assay was performed. NCI-N87 tumor xenograft models wer...Continue Reading

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Citations

Nov 24, 2019·International Journal of Molecular Sciences·Haruka YamaguchiAndreas Evdokiou
Jul 28, 2020·Expert Opinion on Biological Therapy·Shigehiro Koganemaru, Kohei Shitara
Jul 16, 2019·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Takashi NishimuraMasayuki Saruta
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Oct 26, 2021·Immunotherapy·Kohei MatsuokaKazuhide Sato

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Methods Mentioned

BETA
flow cytometry
fluorescence microscopy
protein assay
xenograft
xenografts
Fluorescence
fluorescence imaging
light scattering

Software Mentioned

GraphPad Prism
Image J
GraphPad

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