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2015 – Clinical Sciences and Drug Discovery Abstract – Use of metals as nano-sized radiation enhancers – Pottier et al.

Since the discovery of cisplatin about 40 years ago, the design of innovative metal-based anticancer drugs is a growing area of research. Metal elements offer specific characteristics due to their intrinsic properties and could be used in relation to their final state: a metal complex, a radionuclide, a metal-based nanoparticle product. Transition metal coordination complexes interact with cell molecular targets, affecting biochemical functions resulting in cancer cell destruction. Radionuclides are another way to use metals as anticancer therapy. The metal nucleus of the unstable radionuclide becomes stable by emitting energy. The biological effect in different tissues is obtained by the absorption of this energy from the radiation emitted by the radionuclide, the principal target generally agreed for ionizing radiations being DNA. A new area of clinical research is now emerging using the same experimental metal elements, but in a radically different manner: metals and metal oxides used as crystalline nanosized radiation enhancers particles. The use of metals as a high electron density material tailored at the nanoscale when exposed to radiotherapy is a unique approach that can allow entry to the cell and make feasible the absorption/deposition of a high-energy dose within the tumor cell (on/off activity). Therefore, high electron density metal or metal oxide nanoparticles may bring well known physical mode of action, that of radiotherapy, within malignant cells and achieve the paradigm of local cancer treatment.

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2017 – Immunotherapy Workshop

Radiotherapy (RT) has proven its ability to function like an in-situ vaccine, showing potential for successful combination with immunotherapeutic agents. Hafnium oxide nanoparticle (HfO2-NP), undergoing clinical trials for enhancing RT, was designed as high electron density material at the nanoscale. HfO2-NPs are taken up by cancer cells and, when exposed to RT, locally increase the radiation dose deposit, triggering more cancer cells death when compared to RT. We hypothesized that HfO2-NP+RT could trigger an enhanced immune response when compared to RT, both in preclinical and clinical settings.

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2017 – AACR Abstract – NBTXR3 anti-tumor efficacy in vivo

NBTXR3 has been evaluated in numerous in vivo models. The antitumor efficacy was systematically enhanced in terms of tumor growth delay for animals treated with NBTXR3 and exposed to radiotherapy when compared to radiotherapy alone. In this abstract the transferability of the treatment with NBTXR3 from one type of cancer to the other is described. NBTXR3 is intended to be injected in the tumors. Spilling in the circulation may occur during product administration or, as expected, during tumor destruction, leading to steady trapping of NPs in the reticulo-endothelial system (liver and spleen). Clinically, it is unknown whether patients, previously treated with NPs, may show toxic signs when NPs are exposed (activation) to diagnosis imaging (computed tomography(CT)) of the liver.

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2016 – SITC Abstract – NBTXR3 for in situ cancer vaccination

NBTXR3 exposed to irradiation enhanced cancer cells destruction and immunogenic cell death compared to irradiation alone, suggesting a strong potential for transforming tumor into an effective in situ vaccine. This may contribute to transform “cold” tumor into “hot” tumor and effectively be combined with most of the immunotherapeutic agents across oncology. NBTXR3 is intended to be injected in the tumors. Spilling in the circulation may occur during product administration or, as expected, during tumor destruction, leading to steady trapping of NPs in the reticulo-endothelial system (liver and spleen). Clinically, it is unknown whether patients, previously treated with NPs, may show toxic signs when NPs are exposed (activation) to diagnosis imaging (computed tomography(CT)) of the liver.

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2015 – The future of nanosized radiation enhancers – Pottier et al.

Radiotherapy has a universal and predictable mode of action, that is, a physical mode of action consisting of the deposit of a dose of energy in tissues. Tumour cell damage is proportional to the energy dose. However, the main limitation of radiotherapy is the lack of spatial control of the deposition of energy, that is, it penetrates the healthy tissues, damages them and renders unfeasible delivery of an efficient energy dose when tumours are close to important anatomical structures. True nanosized radiation enhancers may represent a disruptive approach to broaden the therapeutic window of radiation therapy.

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