SUMMARY:
UCLA researchers in the David Geffen School of Medicine have developed a nanocarrier platform to deliver drugs that block CXCR4 directly in tumor microenvironments, with an impact on immune cell trafficking and reducing the tumor’s metastatic burden.
BACKGROUND:
Cancer remains among the leading causes of death worldwide, and its burden is expected to grow from approximately 18 million new cases in 2018 to almost 30 million in 2040. Despite continued progress in limiting mortality with new treatments, including monoclonal antibodies and immunotherapy, the high death rate from cancer is primarily contributed by metastasis and relapse. Increasing evidence points to the key role that cells in the tumor stroma play in tumor initiation, progression, and metastasis. The chemokine CXCR4 has been implicated as a key factor that mediates communication between cancer cells and immune cells in their microenvironment. In fact, CXCR4 is overexpressed in more than 23 human cancers, playing a key role in excluding immune cells from the cancer core and impacting metastatic spread of cancer cells. Thus, developing treatments to disrupt the function of CXCR4 by inhibitory drugs could transform cancer treatment for a wide variety of tumors.
INNOVATION:
UCLA researchers led by Dr. Andre Nel in the School of Medicine have developed lipid bilayer coated nanocarriers for delivery of a CXCR4 antagonist to treat tumors. Using in vivo murine models of pancreatic and breast cancer, they found that the CXCR4 antagonist successfully disrupted tumor-stromal interactions, with reduction of tumor growth and metastasis. The impact of growth reduction included the ability of the antagonists to increase immune cell access to the tumor core and reducing the impact of immune suppressive cells in the tumor microenvironment. Targeted delivery of the CXCR4 antagonist to the tumor microenvironment helped to diminish off-target systemic inflammatory effects. Taken together, a new method to deliver therapeutic agents to tumor microenvironments could reduce mortality of cancers.
POTENTIAL APPLICATIONS:
• Targeted delivery of CXCR4 antagonists to treat pancreatic cancer and triple negative breast cancer, in adjunct to chemo or chemo-immunotherapy
ADVANTAGES:
• The lipid bilayer coated nanocarrier platform allows versatility of also including synergistic therapeutic agents in the lipid bilayer, in addition to CXCR4 antagonist in the carrier interior
• Improved pharmacokinetics of drug delivery
• Reduced off-target effects
• Carrier can be intravenously injected for targeted delivery
DEVELOPMENT-TO-DATE:
This technology was successfully demonstrated to reduce tumor growth in multiple types of tumor murine models, including pancreatic cancer and triple negative breast cancer.
Related Papers (from the inventors only):
Nel AE*, Mei KC, Liao YP, Liu X. Multifunctional Lipid Bilayer Nanocarriers for Cancer Immunotherapy in Heterogeneous Tumor Microenvironments, Combining Immunogenic Cell Death Stimuli with Immune Modulatory Drugs. ACS Nano 2022, 16, 4, 5184–5232.