401P - Enhancing antitumor immunity by photodynamic therapy with gemcitabine in metastatic 4T1 breast tumor.

Date 18 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Metastatic
Presenter Lilach Agemy
Citation Annals of Oncology (2016) 27 (suppl_9): ix123-ix125. 10.1093/annonc/mdw588
Authors L. Agemy, R. Hamri, T. Yechezkel, N. Kudinova, Y. Salomon, A. Scherz
  • Department Of Plant And Environmental Sciences, Weizmann Institute of Science, 7610001 - Rehovot/IL

Abstract

Background

Combination of therapeutic modalities that target the tumor cells and immune suppressor cells constitute a promising avenue for controlling primary tumor growth and successful eradication of metastases. We hypothesized that local tumor ablation by photodynamic therapy (PDT) with STL-6014 (an RGD-coupled bacteriochlorophyll) synchronized with administration of gemcitabine, an anti myeloid derived suppressor cells agent, should significantly improve survival in 4T1 murine metastatic breast cancer mouse model.

Methods

4T1-Luc cells were grafted in the mammary pad. Seven days later, PDT treatment comprised i.v. bolus administration of STL-6014 and tumor illumination at 753 nm at 4h or 6h following STL-6014 administration was performed. Two days before or on the following day and every 5 days till day 30, mice were i.p. injected with gemcitabine (75 mg/kg body). Metastases were assessed by luciferin bioluminescence using IVIS spectrum imaging system.

Results

FACS and tissue immunohistochemistry analyses showed STL-6014 heterogeneous accumulation in cancer cells, endothelial cells, cancer associated fibroblasts, myeloid-derived suppressor cells, and tumor-associated macrophages. Illumination of the 4T1 tumors 4h post STL-6014 administration resulted in complete ablation of primary tumors in up to 70% of the treated mice. Damage to blood vessels followed by apoptotic and necrotic cell death was detected within 24h post PDT. Regardless of successful primary tumor ablation, >80% of the treated animals developed lung metastases at day 28. In contrast, when PDT was combined with gemcitabine, ∼35% of mice were cured 120 days post PDT, while 35-45% developed local recurrence without metastasis and 20-30% had both. Overall, ∼80% of mice in the combined group were metastases free at the day of sacrifice (either due to local recurrence or after 120 days of follow up). The combined treatment blocked splenic elevation of MDSC, Tregs and TAMs and increased DC and CD8 cells populations.

Conclusions

In conclusion, the significant suppress of lung metastasis and increase in cancer free survival in mice bearing metastatic 4T1 tumors following combination treatment provides novel approach for the treatment of triple negative breast cancer.

Legal entity responsible for the study

Weizmann Institute of Science

Funding

The Wade Thompson foundation

Disclosure

All authors have declared no conflicts of interest.