Local and Systemic Antitumor Effects of Photo-activatable Paclitaxel Prodrug on Rat Breast Tumor Models.

Abstract

We demonstrated that a large primary and a small untreated distant breast cancer could be controlled by local treatment with our light-activatable paclitaxel (PTX) prodrug. We hypothesized that the treated tumor would be damaged by the combinational effects of photodynamic therapy (PDT) and locally released PTX and that the distant tumor would be suppressed by systemic antitumor effects. Syngeneic rat breast cancer models (single- and two-tumor models) were established on Fischer 344 rats by subcutaneous injection of MAT B III cells. The rats were injected with PTX prodrug (dose: 1umolekg-1 , i.v.), and tumors were treated with illumination using a 690-nm laser (75 or 140mWcm-1 for 30min, cylindrical light diffuser, drug-light interval [DLI] 9h). Larger tumors (~16mm) were effectively ablated (100%) without recurrence for >90days. All cured rats rejected rechallenged tumor for up to 12months. In the two-tumor model, the treatment of the local large tumor (~16mm) also cured the untreated tumor (4-6mm) through adaptive immune activation. This is our first demonstration that local treatment with our PTX prodrug produces systemic antitumor effects. Further investigations are warranted to understand mechanisms and optimal conditions to achieve clinically translatable systemic antitumor effects.