(714c) Targeted Single-Walled Carbon Nanotubes for Photothermal Ablation of Breast Cancer Combined with Immunostimulation
Mice with well-developed orthotopic syngeneic EMT6 tumors (d â¥ 5 mm) were administered an intravenous systemic dose of the conjugate of single-walled carbon nanotubes (SWNTs) and ANXA5, which localized to tumor vasculature. Tumors were then irradiated with mild laser light using a Diodevet-50 NIR system for 175 s, at a power density of 1 W cm2. Select mice additionally received three doses of 200 Î¼g of the immunostimulant anti-CTLA-4 in order to prime the immune system prior to photothermal therapy. The low energy NIR laser does not harm healthy tissue but rapidly generates temperatures in excess of 60Â° C within the tumor. This temperature is sufficient to instantly destroy cancerous cells. Healthy tissue fails to accumulate the SWNT-ANXA5 conjugate and remains unaffected by the NIR laser. The addition of anti-CTLA-4 immunotherapy in conjunction with this targeted photothermal ablation modality resulted in a significant synergistic increase in helper T cells (CD4+) and cytotoxic/suppressor (CD8+) in the spleen when compared to photothermal or immunostimulatory monotherapy. This increase in tumor effector cells led to tumor rejection. The combination of immunostimulation and targeted photothermal therapy led to significant increases in animal survival with more than half of all animals found to be tumor free at the conclusion of the study (120 days), at which time all of the animals in the control groups had died.