Radiation

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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2017 – A phase 1 trial of NBTXR3 nanoparticles activated by IMRT in the treatment of advanced-stage head and neck carcinoma

Functionalized hafnium oxide nanoparticles (NBTXR3) have been developed as selective radioenhancers, which may represent a breakthrough approach for the local treatment of solid tumors. The high electron density of the nanoparticles, when exposed to radiotherapy (RT), allow the absorption/deposition of a high radiation dose within the tumor cells, to physically kill the cells and possibly improve outcome.

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2017 – Specific adaptive immune pattern induced by NBTXR3 exposed to radiation therapy in soft tissue sarcoma (STS) patients

NBTXR3 are functionalized hafnium oxide nanoparticles, undergoing seven clinical trials for enhancing radiation therapy (RT). The high electron density of the nanoparticles, when exposed to radiotherapy (NBTXR3 + RT), allow absorption/deposition of a high radiation dose within the cancer cells to physically kill the cells, and possibly improve outcome. Besides, NBTXR3 + RT has shown subsequent ability to enhance immunogenic cell death and immune response in preclinics. We hypothesized that NBTXR3 + RT could trigger an enhanced immune response when compared to RT in patients with STS.

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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 – 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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2015 – Metals as radio-enhancers in oncology – Pottier et al.

Radio-enhancers, metal-based nanosized agents, could play a key role in oncology. They may unlock the potential of radiotherapy by enhancing the radiation dose deposit within tumors when the ionizing radiation source is ‘on’, while exhibiting chemically inert behavior in cellular and subcellular systems when the radiation beam is ‘off’. Important decision points support the development of these new type of therapeutic agents originated from nanotechnology. Here, we discuss from an industry perspective, the interest of developing radio-enhancer agents to improve tumor control, the relevance of nanotechnology to achieve adequate therapeutic attributes, and present some considerations for their development in oncology.

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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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2014 – NBTXR3 concept and dose enhancement – Marill et al.

Hafnium oxide, NBTXR3 nanoparticles were designed for high dose energy deposition within cancer cells when exposed to ionizing radiation. The purpose of this study was to assess the possibility of predicting the in vitro the biological effect of NBTXR3 nanoparticles when exposed to ionizing radiation. Cellular uptake of NBTXR3 nanoparticles was assessed in a panel of human cancer cell lines (radioresistant and radiosensitive) by transmission electron microscopy. The radioenhancement of NBTXR3 nanoparticles was measured by the clonogenic survival assay.

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2011 – AACR Abstract – NBTXR3 radioenhancement and anti-tumor effect in vitro – Magiorella et al.

Local and systemic control of Soft Tissue Sarcoma (STS) remains a clinical challenge. Radiation therapy is part of the standard of care of STS. The narrowness of its therapeutic window represents the main concern for different clinical settings. Thus, local delivery of radiation doses is critical to ensure optimal benefit-risk ratio. NBTXR3, biocompatible hafnium oxide nanoparticles were designed as therapeutics to be activated by ionizing radiation to achieve tumor control by enhancement of local energy deposition.

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2010 – Concept of NBTXR3 – Borghi et al.

La nanotechnologie permet une gestion et un assemblage de matériaux sans précédent dans l’histoire des produits utilisés en santé humaine. Cette révolution est apportée par la possibilité d’utiliser de nouveaux mécanismes thérapeutiques et de dissocier les différentes fonctions de la substance médicamenteuse (distribution, effet thérapeutique…), ce qui était jusqu’ici impossible avec les médicaments classiques.

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