The effects of conjugate and light dose on photo-immunotherapy induced cytotoxicity.

Takahito Nakajima,Rira Watanabe,Toshiko Harada,Kazuhide Sato,Hirofumi Hanaoka,Peter L Choyke,Hisataka Kobayashi

doi:10.1186/1471-2407-14-389

Takahito Nakajima, Rira Watanabe + Show 5 more

Open Access

https://doi.org/10.1186/1471-2407-14-389

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Abstract

BackgroundPhotoimmunotherapy (PIT) is a highly cell-selective cancer therapy, which employs monoclonal antibodies conjugated to a potent photosensitizer (mAb-IR700). Once the conjugate has bound to the target cell, exposure to near infrared (NIR) light induces necrosis only in targeted cells with minimal damage to adjacent normal cells in vivo. Herein, we report on the effect of altering mAb-IR700 and light power and dose on effectiveness of PIT.MethodsFor evaluating cytotoxicity, we employed ATP-dependent bioluminescence imaging using a luciferase-transfected MDA-MB-468luc cell line, which expresses EGFR and luciferase. In in vitro experiments, panitumumab-IR700 (Pan-IR700) concentration was varied in combination with varying NIR light doses administered by an LED at one of three power settings, 100 mA and 400 mA continuous wave and 1733 mA intermittent wave. For in vivo experiments, the MDA-MB-468luc orthotopic breast cancer was treated with varying doses of Pan-IR700 and light.ResultsThe in vitro cell study demonstrated that PIT induced cytotoxicity depended on light dose, when the conjugate concentration was kept constant. Increasing the dose of Pan-IR700 allowed lowering of the light dose to achieve equal effects thus indicating that for a given level of efficacy, the conjugate concentration multiplied by the light dose was a constant. A similar relationship between conjugate and light dose was observed in vivo.ConclusionsThe efficacy of PIT is defined by the product of the number of bound antibody conjugates and the dose of NIR light and can be achieve equally with continuous and pulse wave LED light using different power densities.

Highlights

Photoimmunotherapy (PIT) is a highly cell-selective cancer therapy, which employs monoclonal antibodies conjugated to a potent photosensitizer
When the monoclonal antibody (mAb)-IR700 conjugate is well matched to the target tumor, exposure to near infrared (NIR) light results in rapid and severe damage to the cell membrane inducing necrotic cell death within a minute [3]
During continuous NIR light exposure the cells demonstrated almost immediate swelling, budding and rupture of the membrane was observed leading to irreversible cell death (Figure 2)

Summary

Introduction

Photoimmunotherapy (PIT) is a highly cell-selective cancer therapy, which employs monoclonal antibodies conjugated to a potent photosensitizer (mAb-IR700). Once the conjugate has bound to the target cell, exposure to near infrared (NIR) light induces necrosis only in targeted cells with minimal damage to adjacent normal cells in vivo. Photoimmunotherapy (PIT) is a highly cell-selective cancer therapy, which utilizes a monoclonal antibody (mAb) conjugated to the photosensitizing phthalocyanine dye, IRDye700DX (IR700). MAbIR700 conjugates preferentially to cancer cells expressing the proper antigen and subsequent exposure of the cells to near infrared (NIR) light induces highly selective and rapid cell necrosis. When the mAb-IR700 conjugate is well matched to the target tumor, exposure to NIR light results in rapid and severe damage to the cell membrane inducing necrotic cell death within a minute [3]. Optimized dosing of NIR light exposure is critical for planning a successful clinical trial of PIT in both therapeutic efficacy and patient safety

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