Photodynamic therapy (PDT) is FDA-approved for the treatment of several cancer types. However, a lack of efficacy and undesirable toxic side effects associated with many existing photosensitisers has largely restricted their use to superficial tumours. This work presents data characterising a new, non-toxic sensitiser technology - “PhotosoftTM” - as an effective approach for the treatment of solid tumours using a murine orthotopic model.
PhotosoftTMin vitro excitation / emission spectra and singlet oxygen (1O2) production on illumination at 652nm were established in a cell-free system. In ovarian cancer cells PhotosoftTM rapidly localised to the cytoplasm in a time- and concentration-dependent manner, and was retained in lysosomes and endoplasmic reticulum. Exposure to light at 652nm resulted in immediate activation and necrotic cell death. Unlike several other sensitisers tested, no “dark toxicity” (i.e. in the absence of light activation) was observed.
When injected in vivo (syngeneic mouse model of ovarian cancer) PhotosoftTM localised rapidly to tumour tissue (maximal at 1hr), and was retained in tumour tissues (but not healthy tissue) for at least 48 hrs. Activation (light dose 180J/cm2 at 500mW) resulted in substantial inflammation and necrosis of tumour tissue after 2 days, with tumour burden reduced by >50% after 3 weeks. Analyses of immune parameters associated with PDT are ongoing.
Our data establish the first proof-of-principle that PhotosoftTM technology offers a non-toxic and effective in vivo strategy for the ablation of solid tumours. Further work to establish the immune consequences and contribution of anti-tumour immunity to regression are ongoing. This data establishes preliminary evidence supporting ongoing preclinical studies, and progression to first-in-human clinical trials for PhotosoftTM technology as an indication for solid tumour types.