Targeted- and timed-releasing nanotherapeutics to eradicate acute leukemia stem cells

Funding Type: 
Early Translational IV
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 
Acute myeloid leukemia (AML) is the most common acute leukemia in adults with less than 30% of patients cured with current treatment. In most cases, AML cells arise from a group of specialized cells, named leukemia stem cells (LSC). LSC often survive conventional chemotherapy currently used in clinic, regenerate leukemia cells and cause a recurrence of the disease. We recently developed a small molecule that can recognize and bind to AML LSC. We also developed tiny particles named nanomicelles. These nanomicelles have a size of about 1-2/100th of one micron (one millionth of a meter), and can be loaded with chemotherapy drugs that can kill LSC. In this project, we will covalently decorate the drug-loaded nanomicelle surface with the LSC-specific small molecules, enabling delivery of the drug specifically to LSC. In the patient’s body, these drug-loaded nanomicelles will work like “smart bombs”, and deliver a high concentration of chemotherapy drugs to LSC and kill these cells. Furthermore, the chemotherapy drug can be released from nanomicelles to patient’s blood and kill leukemia cells throughout the body. With these nanomicelles, both leukemia cells and LSC are killed, and leukemia can possibly be eradicated at its very root. In addition, formulation of chemotherapeutic drug into nanomicelles could significantly decrease the toxicity. This is clinically significant as 10-15% patients die from the toxicity of the chemotherapy they currently receive.
Statement of Benefit to California: 
Leukemia is the 7th most common cause of cancer death in California. Acute myeloid leukemia (AML) is the most common cause of leukemia death. Over 70% of AML patients will die from this disease or treatment-related complications. These patients usually require costly and highly toxic chemotherapy at the inpatient setting. Many patients die from the complications of treatment. This project aims to develop therapeutic agents that specifically target leukemia stem cells and therefore eradicate leukemia at its root. Furthermore, the agents developed in this project can decrease treatment-related toxicity and death. If this project is successful, it will decrease the need for stem cell transplantation, another treatment modality that is associated with even higher treatment-related mortality and cost. Furthermore, many patients cannot undergo stem cell transplantation because it is often difficult to find matched donors for stem cells. This is especially true in California because of the genetically diversified population. This project may have huge financial benefits to California. Several investigators of this research team have experience in commercializing their discoveries. Three patent applications related to this proposed therapeutics have already been filed. If this project is successful, we will consult the US Food and Drug Administration to bring this drug into clinical applications, and license the patents for commercial development.

© 2013 California Institute for Regenerative Medicine