Abstract 5483: Targeted intracellular photodynamic therapy (TIP) reduces tumor mass and prolongs survival in a mouse model of cancer

Abstract

Targeted Intracellular Photodynamic Therapy (TIP) is a novel advance on traditional photodynamic therapy (PDT) in which photosensitizer activation is afforded by chemiluminescence rather than by laser beam. This advance allows PDT access to target cells essentially anywhere in the body. TIP also has advantages over bioluminescence as there is no need for transfection of cells with enzymes such as luciferase. It can therefore be more easily applied both in vitro and in vivo and has potential as a new targeted cancer therapeutic modality that could be applied to a wide variety of cancers. We have previously described in vitro the efficacy and specificity of TIP toward murine leukemic cells (Brit. J. Cancer, 95; 189-196, 2006). We now report that TIP is effective in vivo using a murine model of cancer. To target the photosensitizer, Protoporphyrin IX was conjugated to Transferrin (Trnsf-PrP). Balb/c mice were injected subcutaneously with the mouse hybridomas U13.6 or U7.6, both of which overexpress the Transferrin receptor CD71. The use of Trnsf-PrP resulted in rapid uptake of photosensitizer into cells and conjugate was retained for over 48hrs. Animals were treated with TIP by injecting Trnsf-PrP and the chemiluminescent agent Luminol (LM) under reduced light conditions. Experiments were performed whereby different parameters of the system were varied, including: time of treatment initiation after tumor cell inoculation; dose and number of Trnsf-PrP and luminol treatments; and time intervals between treatments. Initial experiments in which TIP was performed at the time of tumor inoculation showed that this procedure completely abolished tumor growth. In subsequent experiments where tumors were palpable before treatment began, various treatment protocols were tested. TIP reduced tumor mass by over 40% and increased survival by 50%. These results demonstrate that TIP is active against cancer cells in vivo and encourages the further development of the modality as a targeted cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5483.