Pioneering solid-tumor cancer program
PARIS & CAMBRIDGE, Mass.—NANOBIOTIX, a late-clinical-stage nanomedicine company developing new approaches to treating cancer, is beginning a preclinical collaboration with Portland, Ore.-based Providence Cancer Institute to study NANOBIOTIX’s lead product, NBTXR3, a first-in-class nanoparticle designed for direct injection into cancerous tumors and activation by radiotherapy.
The objective of the collaboration is to deliver preclinical data on the ability of NBTXR3 activated by radiotherapy to induce an antitumoral immune response. It is an in-depth study into the early immunologic mechanisms, triggered by nanoparticles activated by radiotherapy compared to radiotherapy alone, and their impact on tumor control, survival and metastasis spreading.
NBTXR3, an injectable aqueous suspension of hafnium oxide nanoparticles designed as an innovative therapeutic agent for the treatment of solid tumors, is currently in clinical development. Preclinical evaluations observed that NBTXR3 can deposit high energy within tumors only when activated by an ionizing radiation source, notably radiotherapy. Upon activation, the high energy radiation physically kills the tumor cells by triggering DNA damage and cell destruction.
NBTXR3 is characterized by a chemically inert behavior in cellular and subcellular systems, reportedly demonstrating a good local and systemic tolerance, decreasing potential health hazards. Taken together, NBTXR3’s mechanism of action, efficacy and biocompatibility profile indicate a promising oncological application fitting with current clinical radiotherapies, according to the company.
NBTXR3, which entered clinical development in 2011 in a Phase 1/2 study with patients suffering from advanced soft tissue sarcoma of the extremities, is in the final stages of its subsequent Phase 2/3. In parallel, it is being evaluated in numerous Phase 1/2 clinical trials with patients suffering from locally advanced squamous cell carcinoma of the oral cavity or oropharynx, liver cancer, locally advanced or unresectable rectal cancer in combination with chemotherapy, head and neck cancer in combination with concurrent chemotherapy and prostate adenocarcinoma.
Preclinical evaluations have identified NBTXR3’s promising application in the treatment of solid tumors, and it is being clinically assessed in six different oncological indications with encouraging results. The results also indicate that NBTXR3 activity could be applicable across solid tumors: triggering immunogenic cell death (ICD), leading to an immune response, reinforcing a local and potentially systemic effect and contributing to the ability to transform “cold” tumors into “hot” tumors.
NANBIOTIX has studied the ability of nanoparticles activated by radiotherapy (RT) to generate ICD, compared to RT alone, and demonstrated in vitro that on a panel of human cancer cell lines, the ICD is increased for cells treated with nanoparticles activated by RT, compared to RT alone. However, it is possible that nanoparticles activated by RT could use additional pathways and could contribute to the induction of the antitumoral immune response.
Preliminary studies suggest that nanoparticles activated by radiotherapy trigger an antitumor immune response more efficiently than radiotherapy alone, according to the company. These studies are mainly focused on adaptive immunity, which is a relatively “late-stage” element of the whole antitumor immune response. The early immunologic mechanisms are crucial for the fate of tumor progression and will influence (positively or negatively) the capability of the adaptive immune system to destroy cancer cells. By studying these early steps, NANOBIOTIX hopes to shed some light on the differences between radiotherapy and nanoparticles activated by radiotherapy, which could explain the efficacy of the nanoparticles.
Previous in-vitro and in-vivo studies performed on many cancer models have demonstrated that nanoparticles activated by radiotherapy are more efficient than radiotherapy alone to kill cancer cells and control tumor growth. In addition, in-vivo studies in mice show that nanoparticles activated by radiotherapy can produce an abscopal effect, meaning that the local treatment of the tumor can have an effect on a distant site outside of the treatment area. In this model, the company has observed an increase in survival. Based on these results, NANOBIOTIX believes that similar results could be obtained in this project and that a better control of metastasis spreading would be obtained. If so, this may confirm that nanoparticles activated by radiotherapy have the potential to treat metastasis in patients.
The research program will be fully executed by Dr. Marka R. Crittenden, radiation oncologist and director of Translational Radiation Research at the Providence Cancer Institute’s Robert W. Franz Cancer Center, and her team. NANOBIOTIX will provide some of the material needed to carry out the experiments and will support the U.S. team through regular exchanges throughout the program.
Crittenden has significant experience in the field of antitumor immune response, both in research and as a radiation oncologist. Her laboratory masters a model of pancreatic cancer in immunocompetent mice. NANOBIOTIX has developed expertise in the development and use of nanoparticles to treat cancers. Its research team will be able to advise and help Crittenden’s team throughout the project, both for in-vitro and in-vivo experiments.
“Promising preclinical data suggest that nanoparticles combined with radiotherapy enhance tumor-specific immune responses and lead to an abscopal response, priming a patient’s immune system to attack cancer cells outside of the radiotherapy target area,” Crittenden said. “Furthermore, we are absolutely delighted to partner with NANOBIOTIX to advance our research on this phenomenon and the role NBTXR3 can play in immuno-oncology.”
The collaboration is slated to last one year, but it could last longer. “The results from Dr. Crittenden’s team will answer some questions but will probably raise some new ones,” Laurent Levy, CEO and co-founder of NANOBIOTIX, concluded.