NanO2 Enhances Immunotherapy in Triple-Negative Breast Cancers
Abstract
Breast cancer represents an immense threat to women’s and more rarely to men’s health. In particular, metastatic breast cancer represents the highly aggressive form of the disease, accounting for the major cause of patient death since limited treatment options are available, especially those with minimal toxicities. Most of the current therapies are toxic due to their lack of specificity and high dosage required to obtain meaningful stabilization or control of the disease. Hence, there is an urgent unmet need to develop new potential breakthrough treatment strategies and open up a brand-new era of treatment modalities for breast cancers. Although immunotherapy has shown revolutionary results in patients afflicted with melanoma and some types of lung cancers, these results were not obtained in breast cancer patients. Some patients are responders and some are not. It is believed that the difference lies, at least in part, in the immune system of these patients and the way the blood vessels within the tumor may render it highly deprived of oxygen, a condition called hypoxia. Taken together, it is already known that immunotherapy is much less effective in hypoxic tumors. We thus hypothesized that if we reversed the condition of hypoxia, one could address the resistance to immunotherapy. The goals of this study are to develop an innovative therapeutic strategy to better treat breast cancers. Our preliminary results and other recent studies have shown that the product NanO2 (an emulsion of low molecular weight, low boiling point perfluorocarbon, which can load and unload naturally oxygen in places where it is needed) can chemo- and radio-sensitize glioblastomas tumors in animal models and more recently in patients (NuvOx clinical trial phase 1b/2 showed efficacy in radiation treatment of glioblastoma). We have also obtained early preliminary results demonstrating that NanO2 can enhance immunotherapy in a mouse model of breast cancer. Taking in account these scientific premises, the objectives of this proposal are to investigate the effects of NanO2 in breast cancer tumors and to further develop a novel combination strategy for the treatment of aggressive cancers using relevant mouse models of breast cancer such as syngeneic mouse models that naturally produce lung metastases. The ultimate goals are to translate rapidly to the clinical setting this novel therapeutic strategy for the treatment of aggressive breast cancer including triple-negative breast cancers. We have partnered with a clinician who is an expert in breast cancer treatment. We have proposed three specific aims to accomplish this goal: 1. To elucidate the mechanism of action of NanO2 on breast cancer hypoxia and on the immune system in mouse models of breast cancer, 2. To test the combination NanO2 and immunotherapy on breast cancer tumor growth and survival using the same mouse models. Combination with standard chemotherapy and immunotherapy with NanO2 will also be tested for rapid translation to the clinic. 3. To evaluate the safety of the best combination to obtain a complete Investigational New Drug (IND)-briefing package to propose the U.S. Food and Drug Administration (FDA) in preparation of a clinical trial. The overarching challenge for this proposal is to eliminate the mortality associated with breast cancers. Multiple studies indicate that immunotherapy resistance may be due to the condition of hypoxia, which is often exhibited by breast cancers. By also proposing mechanistic studies, we will be able to identify other potential combination strategies that, when combining our product, NanO2, with already known drugs used in the clinic, could have a better outcome for the patient. By working seamlessly with a multidisciplinary team including basic scientists, animal specialists, pathologists, statistician, and a biotech company, we are poised to lead the development of a promising innovative therapeutic strategy for breast cancer treatment. It i
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210639
Entities
People
- Evan Unger
Organizations
- NuvOx Pharma (United States)
- United States Army