Tumor

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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2011 – ECCO Abstract – NBTXR3 as promising cancer therapy – Magiorella et al.

We created and developed NBTXR3 nanoparticles with a crystalline hafnium oxide core which provide high electron density structure and inert behavior in biological media. NBTXR3 nanoparticles’ characteristics, size, charge and shape, allow for efficient interaction with biological entities, cell membrane binding and cellular uptake. The nanoparticles were shown to form clusters at the subcellular level in tumor models. Of most importance, we show NBTXR3 intratumor bioavailability with dispersion of nanoparticles in the three dimensions and persistence within the tumor structure, supporting the use of NBTXR3 as effective antitumor therapeutic agent.

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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 – ESTRO Abstract – hafnium Oxide nanoparticles as anti cancer agent – Deutsch et al.

Nanotechnology is the engineering of objects at the nanometer scale with novel properties. Nanotechnology is being applied to medicine leading to novel diagnostic or treatment applications. Nanoscale objects are about one hundred to ten thousand times smaller than human cells. They are similar in size to large biological molecules ("biomolecules") such as enzymes and receptors. As an example, hemoglobin, the molecule that carries oxygen in red blood cells, is approximately 5 nanometers in diameter. Nanoscale objects smaller than 100 nanometers can move out of blood vessels as they circulate through the body due to morphological features of the endothelium (fenestrae size). Those smaller than 7 nanometers can be cleared from the body by the kidney, as they circulate.

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2017 – Nano-sized cytochrome p450 3a4 inhibitors to block hepatic – Paolini et al.

Most drugs are metabolized by hepatic cytochrome P450 3A4 (CYP3A4), resulting in their reduced bioavailability. In this study, we present the design and evaluation of biocompatible nanocarriers trapping a natural CYP3A4-inhibiting compound. Our aim in using nanocarriers was to target the natural CYP3A4-inhibiting agent to hepatic CYP3A4 and leave drug-metabolizing enzymes in other organs undisturbed.

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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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