Nanobiologic Targeting of Metastatic Breast Tumors: Crossing Multiple Barriers
Abstract
Patients with breast cancer metastases to the brain on average survive less than 1 year. These tumors tend to be resistant to current therapies, and the majority of targeted therapeutics are unable to enter the brain, thus improved alternatives are urgently needed. The objective of the current research is to develop a bio-based therapeutic that can target metastatic breast tumors, including those that have spread to the brain. The design of this nanobiologic also allows it to provide beneficial protection of non-tumor tissue, including neuronal and heart tissue, which are often adversely affected by chemotherapy. The overarching challenges this research aims to address are to (1) revolutionize treatment regimens by replacing interventions that have life-threatening toxicities with ones that are safe and effective and (2) eliminate the mortality associated with metastatic breast cancer. Patients with refractory tumors undergoing metastasis, especially ones that have metastasized to the brain, could benefit from this research. The nanobiologic developed and being tested in this study has the capacity to home to metastatic tumors, including brain metastases, and can eliminate tumor cells while offering protection to non-tumor tissue, including the heart and neuronal tissue. This technology may also have the ability to synergize with existing targeted therapies to corner and eliminate resistant tumor cells, thus preventing recurrence and eventual metastasis. The potential clinical applications of this new technology are to provide patients with a systemic therapy that targets breast cancer metastases, including brain metastases, as well as a treatment for primary tumors that, when used with existing targeted therapies, may prevent recurrence and eventual metastasis. The benefits, if successful, would be reduction or elimination of brain metastatic tumors, for which there are currently no cures, and possible prevention of tumor metastasis after elimination of primary tumors. Additionally, the therapy has the potential to be neuroprotective and cardioprotective, unlike chemotherapy and current targeted therapies, thus not only sparing but possibly protecting a patient’s healthy tissue. This may eliminate the problem of “chemo-brain,” heart damage, and other side effects of cancer therapies. Hence, a patient may re-gain their life back not only in its extension but also improved quality due to maintenance and protection of healthy tissue. A potential risk of this technology is that it may be subverted by the immune system; however, our recent studies suggest that our protein-based nanobiologic uses a strategy we call “ligand mimicry” that implements stealth means to evade immune attack while mimicking an essential ligand for recognition and robust uptake by tumors. Taken together with our total body of work, we anticipate initiating a clinical trial by 2023. Interest and licensing by our biotech spinoff, Eos Biosciences, is enabling scaled-up manufacturing of our protein for eventual testing in collaboration with the pharmaceutical industry. Meanwhile, the current studies proposed in the Expansion Award will contribute to our understanding of the mechanism by which our nanobiologic crosses multiple biological barriers. Our current focus on defining the transport mechanism across the blood-brain barrier will add significant value to the translational development of our nanobiologic toward eventual clinical trials. This research is likely to have a high impact on ending breast cancer because it will address tumors that urgently require an improved therapy, and may contribute to the prevention of such tumors.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910592
Entities
People
- Lali K Medina-Kauwe
Organizations
- Cedars-Sinai Medical Center
- United States Army