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

Autor:	Hu, Yun, Paris, Sébastien, Barsoumian, Hampartsoum, Abana, Chike O., He, Kewen, Sezen, Duygu, Wasley, Mark, Masrorpour, Fatemeh, Chen, Dawei, Yang, Liangpeng, Dunn, Joe D., Gandhi, Saumil, Nguyen, Quynh-Nhu, Cortez, Maria Angelica, Welsh, James W.
Přispěvatelé:	Sezen, Duygu (ORCID 0000-0002-4505-2280 & YÖK ID 170535), Hu, Yun, Paris, Sebastien, Barsoumian, Hampartsoum, Abana, Chike O., He, Kewen, Wasley, Mark, Masrorpour, Fatemeh, Chen, Dawei, Yang, Liangpeng, Dunn, Joe D., Gandhi, Saumil, Nguyen, Quynh-Nhu, Cortez, Maria Angelica, Welsh, James W., School of Medicine
Jazyk:	angličtina
Rok vydání:	2021
Předmět:	Radiation-Sensitizing Agents Lung Neoplasms Biomedical Engineering Pharmaceutical Science Medicine (miscellaneous) Bioengineering Applied Microbiology and Biotechnology Immune memory Mice Nanoparticle Checkpoint blockade Metastatic lung cancer Radioimmunotherapy NBTXR3 Radiation enhancer Radiotherapy Medical technology Animals R855-855.5 Immune Checkpoint Inhibitors Research Neoplasms Experimental Biotechnology and applied microbiology Nanoscience and nanotechnology Science and technology Drug Resistance Neoplasm Nanoparticles Molecular Medicine Female Immunologic Memory TP248.13-248.65 Biotechnology
Zdroj:	Journal of Nanobiotechnology, Vol 19, Iss 1, Pp 1-14 (2021) Journal of Nanobiotechnology
ISSN:	1477-3155
Popis:	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 mu g) and anti-CTLA4 (100 mu g) 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. Cancer Center Support (Core) Grant; Goodwin Family Research Fund; Family of M. Adnan Hamed; Orr Family Foundation; MD Anderson Knowledge Gap Award; Nanobiotix
Databáze:	OpenAIRE
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