SUMMARY:
UCLA researchers in the Department of Medicine have developed a scalable and injectable drug delivery platform that allows for tumor-specific combinatorial cancer immunotherapy treatment of pancreatic cancer.
BACKGROUND:
The National Institute of Health reports that pancreatic ductal adenocarcinomas (PDAC) accounts for at least 90% of all pancreatic cancer cases. PDAC has a five-year survival rate of less than 10% and accounts for over 48,000 deaths per year in the United States, making PDAC one of the most lethal diseases. The high mortality rate is attributed to many factors, including lack of early diagnosis and detection methods, early metastatic spread and, most notably, presence of dysplastic stroma. This dense cellular overgrowth interferes with drug delivery, promotes drug resistance and enhances immune suppressive effects. Irinotecan, a drug commonly used for PDAC chemotherapy, has made a significant impact on improving survival, and shown even greater potential in combination therapy with immune checkpoint inhibitors or toll-like receptor (TLR) agonists. However, irinotecan’s high toxicity limits its efficacy. A targeted drug delivery platform encapsulating irinotecan in combination with othr drug molecules could therefore make further strides in improving patient survival rates against PDAC.
INNOVATION:
UCLA researchers led by Dr. Andre Nel in the Department of Medicine have developed a novel silicasome nanocarrier to improve drug delivery to PDAC and other cancer sites. They designed a nanocarrier that could serve as both a single delivery system, encapsulating lipophilic TLR7 agonist drugs in their lipid bilayer, or a dual drug delivery system, additionally containing irinotecan in the porous aqueous interior. They demonstrated that the silicasome has a higher drug loading capacity than liposomes currently employed in drug delivery therapy. In murine models, the researchers found that their free drug-loaded silicasomes had similar effects on tumor shrinkage as the free drugs, but a markedly stronger response was observed when the drug-loaded silicasomes were injected subcutaneously. Taken together, this technology has unique advantages that can result in impactful clinical responses due to minimal leaking of loaded drugs, improved drug delivery, and reduced systemic toxicity.
POTENTIAL APPLICATIONS:
• Used to increase the therapeutic delivery of known PDAC medications while reducing toxicity effects
• A versatile delivery platform for different types of therapeutics to not only PDAC sites, but other cancer sites as well
• Delivery of TLR agonists or other immune modulatory agents to produce anti-tumor immunogenic responses specifically at tumor sites
ADVANTAGES:
• Increased treatment efficacy for pancreatic ductal adenocarcinomas
• Injectable formula allows for ease of administration
• Structure of silicasome allows for scalability of dual drug carrier system
DEVELOPMENT-TO-DATE:
The UCLA researchers have tested their dual drug-loaded nanocarriers in in vivo murine models and shown great efficacy in tumor shrinkage when the nanocarriers are injected subcutaneously.