| Institution: | 1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK;2. Clinical Pharmacology Program, National Cancer Institute, NIH, Bethesda, MD;3. Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK
Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK;4. Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY |
| 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: 1 umole kg−1, i.v.), and tumors were treated with illumination using a 690-nm laser (75 or 140 mW cm−1 for 30 min, cylindrical light diffuser, drug-light interval DLI] 9 h). Larger tumors (~16 mm) were effectively ablated (100%) without recurrence for >90 days. All cured rats rejected rechallenged tumor for up to 12 months. In the two-tumor model, the treatment of the local large tumor (~16 mm) also cured the untreated tumor (4–6 mm) 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. |
