Prostate | Nano Publications

2019 – ASTRO – NBTXR3 for the treatment of solid tumors

nano-pub — Thu, 19 Sep 2019 13:00:08 +0000

Authors

A. P. Dicker1, C. Shen2, T. De Baere3, C. Hoffmann4, J. W. Welsh5, Y. Rolland6, B. Doger7, R. B. Den1, E. Trabulsi1, C. Lallas1, T. Y. Seiwert8, N. Fernando9, A. Iannessi10, F. Pilleul11, Z. Papai12, R. Tetreau13, P. Rutkowski14, and H. Brisse4

1 – Thomas Jefferson University, Philadelphia, PA
2 – University of North Carolina Hospitals, Chapel Hill, NC
3 – Institut Gustave Roussy, Villejuif, France
4 – Institut Curie, Paris, France
5 – MD Anderson Cancer Center, Division of Radiation Oncology, Houston, TX, 6Centre Eugène Marquis, Rennes, France
7 – START Madrid, Madrid, Spain
8 – Department of Medicine, Section of Hematology/Oncology, The University of Chicago Medicine, Chicago, IL
9 – Northside Hospital, Atlanta, GA
10 – Centre Anticancer Antoine Lacassagne, Nice, France
11 – Unicancer – Leon Berard Cancer Center, Lyon, France
12 – Magyar Honvedseg Egeszsegugyi Kozpont, Budapest, Hungary
13 – Montpellier Cancer Institute, Montpellier, France
14 – Centrum Onkologii-Instytut im. Sklodowskiej-Curie w Warszawie, Warszawa, Poland

Summary

Purpose/Objective(s): Local interventional treatments of cancers include interventional radiology and radiotherapy (RT). NBTXR3, hafnium oxide nanoparticles, is deeply associated to both. Given as a single local administration it increases energy dose deposit inside tumor cells only when activated by ionizing radiation. Various interventional treatments have been used to treat cancers such as liver, lung, bone. Because entirely new therapies such as NBTXR3 are being introduced, implementation of interventional approaches is continuously growing.

Materials/Methods: NBTXR3 is being evaluated in soft tissue sarcoma (STS, extremity, trunk wall) [NCT02379845], head and neck (HN) [NCT01946867, NCT02901483], prostate [NCT02805894], liver [NCT02721056] and rectal cancers [NCT02465593]. NBTXR3 injected volume is a percentage of baseline tumor volume, and therefore heterogeneous. Image guidance allowed for accurate injection. Standard catheters, needles, and syringes were used for preparation and injection. Importantly, percutaneous needle positioning was done within the region to be irradiated to control potential seeding of cancer cells. NBTXR3 was then activated by IMRT (STS, HN), EBRT or combination brachytherapy/EBRT boost (prostate), SBRT (liver), IMRT or IMAT (rectum).

Results: Thus far, NBTXR3 has been administered to 171 patients by intratumoral/lesional, and intraprostate injections depending on indication. NBTXR3 injections have been demonstrated safe and very well tolerated. Local infection, ulceration or massive tumor necrosis were never observed. This has been confirmed by adequate application of treatment schedules, fitting planned irradiation onset 1 to 5 days post-injection. Importantly, grade 1 ecchymosis and hematoma at puncture site (needle entry) observed in few cases always resolved spontaneously and did not impact dosimetry. Indeed, change of tumor/lesion/prostate volume resolved when water (NBTXR3 vehicle) was drained via lymphatic system. So far, inflammatory response to injection procedure itself was mild. Concerning AEs, grade 3 pain was observed in conscious patients under local anesthesia with STS close to joints (limited extensibility), and in needle shift in injection within a subcapsular liver tumor.

Conclusion: Across 7 clinical trials involving tumors in extremity, trunk wall, liver, rectum, prostate and HN, NBTXR3 injection was well tolerated and demonstrated a very good safety profile. The savoir faire of interventional radiology for local treatment of cancers supported implementation of injection procedures with specific parameters according to anatomy. Intratumoral/lesional or intraprostate injection ensures optimum bioavailability at site of irradiation, protecting patients from systemic toxicity. Future clinical research will involve other anatomical sites such as lymph nodes and lung lesions [NCT03589339].

The post 2019 – ASTRO – NBTXR3 for the treatment of solid tumors first appeared on Nano Publications.

2017 – Abstract – 35th CFS – Hafnium Oxide Nanoparticles: An Emergent Promising Treatment for Solid Tumors

nano-pub — Tue, 03 Apr 2018 10:15:38 +0000

Authors

L. Levy1, C. Le Tourneau2, P. Sargos3, Le Pechoux4, G. Kantor3, T. De Baere4, A. Le Cesne4, V. Moreno5, E. Calvo5, S. Bonvalot2

1 – Nanobiotix, Paris, France
2 – Institut Curie, Paris, France
3 – Institut Bergonié, Bordeaux, France
4 – Institut Gustave Roussy, Villejuif, France
5 – START Madrid, Spain

Summary

The enclosed abstract was presented at the 35th Annual Chemotherapy Foundation Symposium, New York. The abstract Hafnium oxide nanoparticles: an emergent promising treatment for solid tumors describes the story of hafnium oxide nanoparticles, NBTXR3, from the preclinical to the clinical development up to date.

Preclinical studies have demonstrated increase of cancer cells death in vitro and marked antitumor efficacy in vivo in presence of these nanoparticles (HfO2-NP) exposed to RT, when compared to RT alone. Hafnium oxide nanoparticles efficacy was assessed in cancer epithelial and mesenchymal tumor models and on patient-derived tumor xenografts in nude mice, showing superior anti-tumor effects, over radiation therapy alone in terms of complete response and overall survival. Additionally, in vivo cancer epithelial models in immunocompetent mouse have showed that HfO2-NP + RT triggers immunogenic conversion of the tumor microenvironment and generate an abscopal effect while this effect is not observed with RT alone.

HfO2-NP (NBTXR3), administered as a single intratumoral injection and activated by radiotherapy, is currently evaluated in clinical trials including soft tissue sarcoma (STS) [NCT02379845], head and neck [NCT01946867], prostate [NCT02805894], liver [NCT02721056; NCT02721056] and rectum cancers [NCT02465593]. Patients treated in phases I have had a good tolerance to the product and received radiotherapy as planned, confirming a very good local safety profile.

Besides, consistently with non-clinical studies, preliminary results of the phase II/III in patients with STS, beyond the expected cytotoxic effect induced by NBTXR3 + RT, suggest a release of tumor neoantigens during cancer cell death and stimulation of local immunological effects. This immunogenic cell death might convert “cold” tumor into “hot” tumor. Further analyses are ongoing to reinforce these findings.

The post 2017 – Abstract – 35th CFS – Hafnium Oxide Nanoparticles: An Emergent Promising Treatment for Solid Tumors first appeared on 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.

The post 2017 – Abstract SITC Conference Maryland – Non Clinical first appeared on Nano Publications.

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.

The post 2017 – Abstract Conference Immunotherapy Radiotherapy Combinations NYC first appeared on Nano Publications.