A radioenhancing nanoparticle mediated immunoradiation improves survival and generates long-term antitumor immune memory

J Nanobiotechnology, 2021 · Hu Y, Paris S, Barsoumian H, Abana CO, He K, Sezen D, et al.


Yun Hu1, Sébastien Paris2, Hampartsoum Barsoumian1, Chike O. Abana1, Kewen He1,3, Duygu Sezen1,4, Mark Wasley1, Fatemeh Masrorpour1, Dawei Chen3, Liangpeng Yang1, Joe D. Dunn1, Saumil Gandhi1, Quynh-Nhu Nguyen1, Maria Angelica Cortez1 and James W. Welsh1

1 – Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 6565 MD Anderson Boulevard, Houston, TX 77030 USA
2 – Department of Translational Science, Nanobiotix, Paris, France
3 – Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
4 – Department of Radiation Oncology, Koc University School of Medicine, Istanbul, Turkey


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 in which NBTXR3, a clinically approved nanoparticle radioenhancer, is combined with high-dose radiation (HDXRT) to a primary tumor plus low-dose radiation (LDXRT) to a secondary tumor along with checkpoint blockade in a mouse model of anti-PD1-resistant metastatic lung cancer.

Methods: Mice were inoculated with 344SQR cells in the right legs on day 0 (primary tumor) and the left legs on day 3 (secondary tumor). Immune checkpoint inhibitors (ICIs), including anti-PD1 (200 μg) and anti-CTLA4 (100 μg) were given intraperitoneally. Primary tumors were injected with NBTXR3 on day 6 and irradiated with 12-Gy (HDXRT) on days 7, 8, and 9; secondary tumors were irradiated with 1-Gy (LDXRT) on days 12 and 13. The survivor mice at day 178 were rechallenged with 344SQR cells and tumor growth monitored thereafter.

Results: NBTXR3 + HDXRT + LDXRT + ICIs had significant antitumor effects against both primary and secondary tumors, improving the survival rate from 0 to 50%. Immune profiling of the secondary tumors revealed that NBTXR3 + HDXRT + LDXRT increased CD8 T-cell infiltration and decreased the number of regulatory T (Treg) cells. Finally, none of the re-challenged mice developed tumors, and they had higher percentages of CD4 memory T cells and CD4 and CD8 T cells in both blood and spleen relative to untreated mice.

Conclusions: NBTXR3 nanoparticle in combination with radioimmunotherapy significantly improves anti-PD1 resistant lung tumor control via promoting antitumor immune response.

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