A radioenhancing nanoparticle mediated immunoradiation improves survival and generates long-term antitumor immune memory in an anti-PD1-resistant murine lung cancer model

• DOI: 10.1186/s12951-021-01163-1
• Publication Date: 2021-12-11T20:02:28Z
• Authors: Yun Hu; Sébastien Paris; Hampartsoum Barso...; Chike O. Abana; Kewen He; Duygu Sezen; Mark Wasley; Fatemeh Masrorpour; Dawei Chen; Liangpeng Yang; Joe D. Dunn; Saumil Gandhi; Quynh-Nhu Nguyen; Maria Angelica Co...; James W. Welsh
• Keywords: Immune checkpoint; Primary tumor

Abstract Background Combining radiotherapy with PD1 blockade has had impressive antitumor effects in preclinical models of metastatic lung cancer, although anti-PD1 resistance remains problematic. Here, we report results from a triple-combination therapy which NBTXR3, clinically approved nanoparticle radioenhancer, is combined high-dose radiation (HDXRT) to primary tumor plus low-dose (LDXRT) secondary along checkpoint mouse model anti-PD1-resistant cancer. Methods Mice were inoculated 344SQR cells the right legs on day 0 (primary tumor) and left 3 (secondary tumor). Immune inhibitors (ICIs), including (200 μg) anti-CTLA4 (100 given intraperitoneally. Primary tumors injected NBTXR3 6 irradiated 12-Gy days 7, 8, 9; 1-Gy 12 13. The survivor mice at 178 rechallenged growth monitored thereafter. Results + HDXRT LDXRT ICIs significant against both tumors, improving survival rate 50%. profiling revealed that increased CD8 T-cell infiltration decreased number regulatory T (Treg) cells. Finally, none re-challenged developed they higher percentages CD4 memory blood spleen relative untreated mice. Conclusions combination radioimmunotherapy significantly improves resistant control via promoting immune response. Graphical