Vaccination | Nano Publications

2017 – Abstract SITC Conference Maryland – Non Clinical

nano-pub — Tue, 07 Nov 2017 07:50:03 +0000

Authors

Sébastien Paris, Audrey Darmon, Ping Zhang, Maxime Bergère, Laurent Levy
Nanobiotix, 60 rue de wattignies, 75012 Paris, France

Summary

Background: Hafnium oxide, an electron-dense material, was designed at the nanoscale to increase the radiation dose deposited from within the cancer cells: “Hot spot” of energy deposit where the nanoparticles are when exposed to radiation therapy (RT). Preclinical studies have demonstrated increase of cancer cells killing in vitro and marked antitumor efficacy in vivo with presence of these nanoparticles (HfO2-NP) exposed to RT, when compared to RT alone. […]

Material and Methods: CT26 (murine colorectal cancer cells) were subcutaneously injected in the flank of BALB/c mice. Once the mean tumors volume reached 115±30 mm3, tumors were intratumor injected with HfO2-NP and irradiated with 2Gyx3 or 4Gyx3, or irradiated only. Tumors were collected 5 days after the last RT fraction and analyzed for immune cell infiltrates by immunohistochemistry (2Gyx3 and 4Gyx3) and cytokines content by flow cytometry (2Gyx3). […]

Results: In mice bearing CT26 tumors, a marked increase of cytokines content and immune cell infiltrates was observed with HfO2-NP + 2Gyx3 when compared to RT alone. The tumor immune cell infiltrates were
further enhanced with HfO2-NP + 4Gyx3. In mice inoculated with 4T1 cells treated with HfO2-NP + 40Gy, a marked increase of immune cell infiltrate (CD8+) was observed in tumors when compared to tumors in mice inoculated with 4T1 cells treated with 40Gy and control.

Conclusions: These in vivo data generated from CT26 and 4T1 tumor models suggest that HfO2-NP + RT triggers immunogenic conversion of the tumor microenvironement when compared to RT alone. HfO2-NP treatment may represent a therapeutical approach for broad applications since it does not rely on any molecular characteristics of the tumor.

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2017 – Abstract Conference Immunotherapy Radiotherapy Combinations NYC

nano-pub — Tue, 07 Nov 2017 08:18:59 +0000

Authors

Sébastien Paris, Ping Zhang, Audrey Darmon, Julie Marill, Naeemunnisa Mohamed Anesary, Laurent Levy
Nanobiotix, 60 rue de wattignies, 75012 Paris, France

Summary

Background: Radiation therapy (RT) has demonstrated ability to augment antitumor immunity, promoting immunogenic cell death (ICD) and stimulating immune adjuvant effects. On the other hand, RT has also been reported to induce immunosuppressive responses. A new class of material with high electron density, hafnium oxide, was designed at the nanoscale (HfO2-NP) to efficiently absorb ionizing radiation and augment the radiation dose
deposited from within the tumor cells. […]

Methods: The potential ability of HfO2-NP exposed to RT to transform tumors into immunologically active lesions was tested in vitro and in vivo. In vitro, the level of ICD markers was evaluated in a panel of human cancer cell lines, following cells treated or not with HfO2-NP and irradiated. In vivo, a vaccination assay was performed to evaluate the host immune responses in immunocompetent mice inoculated with murine CT26 cancer cells treated or not with HfO2-NP and irradiated with 6 Gy. […]

Results: Higher DAMPs levels (cell surface expression of calreticulin, extracellular adenosine triphosphate level and extracellular high-mobility group box 1 level) were observed in the tested cancer cells treated with HfO2-NP + RT when compared to cancer cells exposed to RT. […]

Conclusions: These results suggest an efficient cell killing (ability to generate ICD) with superior potential of HfO2-NP + RT to transform the tumor into an effective in situ vaccine when compared to RT. Moreover, HfO2-NP treatment generates a marked increase of immune cells infiltration in the tumors suggesting that it may convert immunologically “cold” tumor into “hot” tumor and could be combined with immunotherapeutic agents across oncology.

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