2020 – Int J Nanomedicine NBTXR3 Induces Abscopal Effect

nano-pub — Tue, 30 Jun 2020 06:54:26 +0000

Authors

Ping Zhang, Audrey Darmon, Julie Marill, Naeemunnisa Mohamed Anesary, Sébastien Paris
Nanobiotix, 60 rue de wattignies, 75012 Paris, France

Summary

Purpose: Despite tremendous results achieved by immune checkpoint inhibitors, most patients are not responders, mainly because of the lack of a pre-existing anti-tumor immune response. Thus, solutions to efficiently prime this immune response are currently under intensive investigations. Radiotherapy elicits cancer cell death, generating an antitumor-specific T cell response, turning tumors in personalized in situ vaccines, with potentially systemic effects (abscopal effect). Nonetheless, clinical evidence of sustained anti-tumor immunity as abscopal effect are rare.

Methods: Hafnium oxide nanoparticles (NBTXR3) have been designed to increase energy dose deposit within cancer cells. We examined the effect of radiotherapy-activated NBTXR3 on anti-tumor immune response activation and abscopal effect production using a mouse colorectal cancer model.

Results: We demonstrate that radiotherapy-activated NBTXR3 kill more cancer cells than radiotherapy alone, significantly increase immune cell infiltrates both in treated and in untreated distant tumors, generating an abscopal effect dependent on CD8+ lymphocyte T cells.

Conclusion: These data show that radiotherapy-activated NBTXR3 could increase local and distant tumor control through immune system priming. Our results may have important implications for immunotherapeutic agent combination with radiotherapy.

The post 2020 – Int J Nanomedicine NBTXR3 Induces Abscopal Effect first appeared on Nano Publications.

2020 – ASTRO – NBTXR3 in Combination with Anti-PD-1

nano-pub — Thu, 17 Dec 2020 17:37:36 +0000

Authors

Colette Shen1, Jessica Frakes2 Jared Weiss1, Jimmy Caudell2, Trevor Hackman1, Jason A. Akulian1, Ghassan El-Haddad2, Robert Dixon1, Yun Hu3, Alexander Pearson4, Hampartsoum B. Barsoumian3, Maria Angelica Cortez3, Katherine Jameson5, Patricia Said5, James Welsh3 and Tanguy Seiwert6

1 – University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
2 – Moffitt Cancer Center, Tampa, Florida, USA
3 – Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA
4 – University of Chicago Medicine, Chicago, Illinois, USA
5 – Nanobiotix, SA, France; 6Johns Hopkins Medicine, Baltimore, Maryland, USA

Summary

Purpose/Objectives: Immune checkpoint inhibitors (ICIs) are being increasingly used to improve patient outcomes across different cancer types. However, the response rate to ICIs remains low (~15%), indicating the need for novel strategies to improve treatment outcome. Emerging evidence suggests that radiation therapy (RT) could potentially enhance the antitumor response and provide synergy with ICIs. RT dose and ultimate efficacy are however limited by toxicity related to exposure of healthy tissues. The first-in-class radioenhancer NBTXR3, administered by direct intratumoral injection, is designed at the nanoscale to increase RT dose deposition within tumor cells and RT-dependent tumor cell killing, without increasing toxicity to surrounding normal tissue. Preclinical and early clinical data suggest NBTXR3 activated by RT can trigger an anti-tumor immune response, producing both local and systemic (abscopal) effects. We hypothesize that NBTXR3 activated by RT, in combination with anti-PD-1 therapy (R3/RT/PD-1), will act synergistically to maximize the local RT effect and produce a systemic response sufficient to increase the proportion of ICI responders or convert ICI non-responders to responders.

Materials/Methods: This multicenter, open-label, phase I trial [NCT03589339] will evaluate safety and tolerability of R3/RT/PD-1 in three cohorts: (1) Locoregional recurrent or recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) amenable to re-irradiation of the HN field, (2) Lung metastases, or (3) Liver metastases, both from any primary cancer eligible for anti-PD-1 treatment. Approximately two-thirds of patients in each cohort will be anti-PD-1 non-responders. NBTXR3 injected volume is based on a percentage of baseline gross tumor volume (GTV).

Results: The primary objective is to determine the R3/RT/PD-1 recommended phase 2 dose in each cohort. Secondary objectives are to evaluate anti-tumor response (objective response rate; ORR), safety and feasibility of NBTXR3 injection, and NBTXR3 body kinetic profile. Exploratory objectives will assess biomarkers of R3/RT/PD-1 response, including PD-L1 status by IHC, as well as mRNA and cytokine immune marker profiling. Recruitment is ongoing. To date, three patients have been treated, one in cohort 1 and two in cohort 2.

Conclusions: NBTXR3 activated by RT induces an anti-tumor immune response which may convert immunologically “cold” tumors into “hot” tumors. In combination R3/RT/PD-1 holds the potential to increase the proportion of ICI responders or convert ICI non-responders to responders.

The post 2020 – ASTRO – NBTXR3 in Combination with Anti-PD-1 first appeared on Nano Publications.

Immune Therapy | Nano Publications

2020 – Int J Nanomedicine NBTXR3 Induces Abscopal Effect

Authors

Summary

2020 – ASTRO – NBTXR3 in Combination with Anti-PD-1

Authors

Summary