NBTXR3 generates an anti-tumor immune reponse

ASTRO, Chicago · 2019, J. O. Thariat et al.

Authors

J. O. Thariat1, M. Lae2, S. Carrere3, Z. Papai4, A. Ducassou5, P. Rochaix6,
Z. Sapi7, I. Peyrottes8, C. Shen9, N. Fernando10, B. A. Perez11, T. Y. Seiwert12, M. C. Chateau13, M. P. Sunyach14, P. Agoston15, H. Brisse2, C. Llacer16, A. Lecesne17, S. Bonvalot2

1 – Centre Franc¸ois Baclesse, Caen, France
2 – Institut Curie, Paris, France
3 – Montpellier Cancer Institute, Montpellier, France
4 – Magyar Honvedseg Egeszsegugyi Kozpont, Budapest, Hungary
5 – Institut Claudius Regaud – IUCT Oncopôle, Toulouse France
6 – Institut Claudius Regaud, Toulouse, France
7 – Semmelweis University, Budapest, Hungary
8 – Centre Anticancer Antoine Lacassagne, Nice, France
9 – Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
10 – Northside Hospital, Atlanta, GA, USA
11 – H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
12 – Department of Medicine, Section of Hematology/Oncology, The University of Chicago Medicine, Chicago, IL, USA
13 – Centre Claudius Regaud, Toulouse, France
14 – Centre Leon Berard, Lyon, France
15 – National Institute of Oncology, Budapest, Hungary
16 – Institut du cancer de Montpellier, Montpellier, France
17 – Institut Gustave Roussy, Villejuif, France

Summary

Purpose/Objective(s): Hafnium oxide nanoparticles (NBTXR3) activated by radiotherapy (RT) increase radiation dose deposit within cancer cells compared to RT alone. Currently 7 clinical trials are underway to evaluate NBTXR3+RT. To date, no dose limiting toxicities (DLTs) have been observed. Given that RT can prime an anti-tumor immune response we hypothesized that this response could be enhanced by NBTXR3+RT in both animals and humans.

Materials/Methods: Immunocompetent mice were injected in both flanks with CT26 cells. An intratumoral injection of NBTXR3 (or vehicle) was performed in right flank tumors, followed by RT (3x4Gy). Tumor growth was followed, and animals sacrificed when tumors reached 800mm3. Alternatively, tumors were collected 3 days after last RT fraction and immune cell infiltrates analyzed by immunohistochemistry (IHC). Pts with locally advanced soft tissue sarcoma (STS) [NCT02379845] received
either NBTXR3+RT or RT alone. Pre- and post-treatment tumor tissues (biopsy and tumor resection respectively) from pts were analyzed by IHC
and Digital Pathology for immune biomarkers (>16 pts per arm).

Results: Animal studies demonstrated that NBTXR3+RT can induce an immune response which was not observed with RT alone. IHC analyses showed that significantly more CD8+ cells were present in NBTXR3+RT treated and untreated tumors, compared to tumors from mice treated with RT alone. Similarly, increased CD8+ T cell infiltration pre- vs post-treatment was observed in tumor tissues from STS pts treated with NBTXR3+RT. An increase in biomarkers, including CD8 and PD1, following NBTXR3 +RT was also observed by IHC in tumor samples from STS pts compared to RT alone.

Conclusion: These results demonstrate that NBTXR3+RT induces a specific adaptive immune profile in both mice and STS pts. As such, it may convert immunologically “cold” tumors into “hot” tumors, opening the potential for combination with immunotherapeutic agents. We have therefore sought to investigate the safety and systemic effect of NBTXR3 activated by stereotactic ablative radiotherapy (SABR) in combination with anti-PD-1 antibody in pts with locoregionally recurrent or metastatic (to lung or liver) head and neck squamous cell carcinoma (HNSCC), as well as in metastatic non-small cell lung cancer (NSCLC) and liver metastasis patients [NCT03589339].

By continuing to use the site, you agree to the use of cookies.En poursuivant votre navigation sur ce site, vous acceptez l’utilisation de cookies. More information.En savoir plus.

The cookie settings on this website are set to “allow cookies” to give you the possibility to switch between languages in a way that this will not interfere with page navigation. If you continue to use this website without changing your cookie settings or you click “Accept” below then you are consenting to this.Par défaut, les paramètres de ce site autorisent les cookies pour vous permettre notamment de naviguer entre les différentes langues disponibles. Nous utilisons des cookies pour vous proposer un site internet facile d'utilisation, sécurisé et fonctionnel. Si vous les autorisez également, cliquez sur « Accepter » ou poursuivez simplement votre navigation.

CloseFermer