The effects of conjugate and light dose on photo-immunotherapy induced cytotoxicity
Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Bldg. 10, Room B3B69, MSC 1088, Bethesda, Maryland 20892-1088, USA
BMC Cancer 2014, 14:389 doi:10.1186/1471-2407-14-389Published: 30 May 2014
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. Herein, we report on the effect of altering mAb-IR700 and light power and dose on effectiveness of PIT.
For 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.
The 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.
The 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.