Non-intuitive combination of drug delivery carriers of the same drug for synergistic growth delay of solid tumors
JHU Ref #: C15411
Unmet Need
Cancer is the second leading cause of death in the United States, with an estimated 1.8 million cases having been diagnosed and 606,520 people having succumbed to the disease in 2020. The most common cancer diagnosis overall and for women is breast cancer, and the most common cancer diagnosis for men is prostate cancer. Although the 5-year relative survival rates for both cancers are high in localized/non-metastatic cases, the survival rates dramatically decrease in metastatic cases (27% for breast cancer and 31% for prostate cancer). Moreover, about 20-30% of prostate cancer patients show signs of recurrence at some point in their lives, and 46.1% of breast cancer patients die after a local recurrence within 10 years. Metastatic and recurrent solid cancers present significant clinical challenges, partly due to the development of therapeutic resistance which limits the available treatment options for these patients.
Alpha-particle radiopharmaceutical therapy (αRPT) has emerged as a promising choice for difficult-to-treat cancers, as the high killing efficacy of alpha particles limits the development of resistance. While alpha particle therapy has been effective in treating disseminated small metastases, it has shown limited efficacy in treating established lesions due to its diffusion-limited penetration depths and the short range of irradiation. Thus, novel solutions are urgently needed to enable uniform and prolonged exposure of the entire tumor to alpha particles in order to effect potent and durable cancer cell killing.
Technology Overview
The inventors at Johns Hopkins have developed a novel nanotechnology platform, a novel approach to irradiation of the deep parts of solid tumors, and a novel transport-driven strategy to enable uniform and prolonged irradiation of the entire volume of solid tumors. The nanoparticle (NP) platform has adhesion properties that bind to the tumors’ extracellular matrix, increasing tumor uptake of NPs and delaying NP clearance from tumors in vivo. Additionally, the platform allows for trigger-release of drugs from the NPs while within the tumor interstitium. This platform is designed to carry alpha-particle emitters, which allows uniform irradiation of the deep parts of the tumor and maximization of emitted energy retention. Moreover, the inventors’ unique transport-driven strategy combines their novel NP platform with established targeting modalities based on the complementarity of their individual tumor micro-distributions. Collectively, this strategy enables uniform and prolonged exposure of the entire tumor to deadly irradiation. This is the first-in-field approach to address the efficacy-limiting heterogenous micro-distributions of alpha-particle emitters in established solid tumors, particularly in breast and prostate solid tumors.
Publication
Zhu et al., Biomaterials 130, 67-75, 2017
U. S. Patent application
