UCLA researchers in the Department of Bioengineering have developed a novel cancer treatment using a combination of microneedle patch-assisted cold atmospheric plasma and checkpoint blockade.
BACKGROUND:
Immunotherapy revolutionizes cancer treatment by harnessing the power of the immune system for fighting cancer. Among all immunotherapeutic strategies, checkpoint inhibitors that block the programmed death-1 (PD1)/programmed death-ligand 1 (PDL1) pathway demonstrate a powerful anticancer potency. Although many exciting outcomes have been witnessed in clinical studies, several barriers that hinder further applications of cancer immunotherapy still need to be resolved, such as low objective rate and systemic side effect. Local delivery of checkpoint inhibitors to the sites of interest is a desirable strategy to minimize or eliminate limitations of immune checkpoint blockade while improving the therapeutic index. On the other hand, cold atmospheric plasma (CAP), a near room temperature ionized gas, has demonstrated the ability to induce cell death, attributed to the elevated reactive oxygen/nitrogen species (ROS/RNS). These immunogenic cell deaths can promote tumor-antigen up-take by dendritic cells (DCs), thereby activating the tumor-specific immune system. Therefore, CAP in combination with checkpoint inhibitors serves as promising treatment for cancer.
INNOVATION:
UCLA scientists in the Department of Bioengineering have developed a novel cancer treatment using a combination of microneedle patch-assisted cold atmospheric plasma and checkpoint blockade. Microneedles (MN) have been widely explored in transdermal drug delivery with minimal patient noncompliance. Since skin is an active protective barrier serving as the immune surveillance system, the hollow structured MN patch can painlessly pierce into the skin and facilitate the delivery of CAP (ROS/RNS) into the tumor sites. The researchers have demonstrated that hollow structured MN can facilitate plasma delivery. The in situ generated immunogenic cell death by CAP led to DC maturation, which promoted T cell infiltration into tumor sites. The combination of CAP and checkpoint blockade triggered strong tumor-specific immunological responses with the help of locally released aPDL1 to eliminate cancer cells. The in vivo studies in the tumor-bearing mice showed that a single treatment of CAP with aPDL1-loaded MN exhibited superior antitumor efficacy.
POTENTIAL APPLICATIONS:
• Cancer treatment
ADVANTAGES:
• Minimally invasive delivery via microneedles
• Precise local delivery to tumor sites
• Facilitate the maturation of dendritic cells and T cell infiltration into tumor sites
• Strong tumor-specific immunological responses elicited by the combination of CAP and checkpoint blockade
DEVELOPMENT-TO-DATE:
The study has been validated in mice.