Sungkyun Institute for Nanoscience and Technology (SAINT) Professor Lim Yong taik's research team (first author Shin Hong sik, a doctoral student) has developed a Toll-like receptor 7/8 agonist (TLR 7/8a) adjuvant that can convert the immunosuppressive environment of the tumor microenvironment into an immune-activating environment with minimal toxicity. toll-like receptor agonist adjuvant was developed. In particular, the immune tolerance phenomenon associated with TLR 7/8a was overcome through molecular and macroscale coordination of the drug delivery system, thereby exceeding the limitations of existing Toll-like receptor 7/8 agonists.The research group also used the principles to overcome the limitations of current macrophage-based cell therapy by conjugating TLR 7/8a onto macrophage cells through click chemistry. 

TLR 7/8a have received attention for their ability to modulate not only innate immune activation but also the immunosuppressive environment of the tumor microenvironment, but they face great difficulties in actual clinical application due to their unique systemic toxicity and immune tolerance. .

To overcome these limitations, Professor Lim Yong taik’s research team developed Nanoliposome(pro-TLR7/8a) (NL(pro-TLR7/8a)), a new concept adjuvant material that can overcome both systemic toxicity and immune tolerance phenomenon through molecular-scopic and macroscopic coordination of drug delivery systems.

NL (pro-TLR7/8a) molecular-scopically masks the point of action of the Toll-like receptor 7/8 agonist molecule with a cholesterol molecule, thereby minimizing the toxicity problem of non-specific action, and in a specific environment, the masked cholesterol gradually recovered to a toll-like receptor 7/8 agonist. It is a drug delivery vehicle that can gradually recover the original activity of the receptor 7/8 agonist and overcome the immune tolerance response caused by an excessive immune response.

NL(pro-TLR7/8a) modulates the immunosuppressive environment of the tumor microenvironment into an immune active environment, promoting continuous secretion of immune active cytokines (interleukin 12, interferon gamma) and minimized immune active cytokines (interleukin 6) in the blood, which are indicators of systemic toxicity.

NL(pro-TLR7/8a) showed excellent therapeutic effects in several tumor models (skin cancer, lung cancer, breast cancer) and achieved complete tumor regression in combination treatment with the immune checkpoint inhibitors anti-PD-1 and anti-CTLA-4.

Combination therapy with Doxorubicin, an anticancer drug currently applied clinically, also showed excellent therapeutic effects, showing high potential for clinical application.

Article Name : Molecular Masking of Synthetic Immunomodulator Evokes Antitumor Immunity with Reduced Immune Tolerance and Systemic Toxicity by Temporal Recovery of Activity and Sustained Stimulation (Advanced Material (IF=32.086), Oct 30, 2023)

Author : Hong sik Shin (1^st author, Ms, Ph.D integrated student), Sohyun Kim (Co-1^st author, Ph.D), Seung Mo Jin (Co-author, Ph.D student), Yeon Jeong Yoo (Co-author, Ph.D student), Janghun Heo (Co-author, Ms, Ph.D integrated student) and Yong Taik Lim (Corresponding author, Sungkyunkwan Uni. Prof.)

Article Name : Nanoengineered Macrophages Armed with TLR7/8 Agonist Enhance Remodeling of Immunosuppressive Tumor Microenvironment (Small (IF : 15.153), Nov 15, 2023)

Author : Yeon Jeong Yoo (1^st author, Ph.D student), Suhyun Kim (Co-author, Ms student), Sei Hyun Park (Co-author, Ph.D student), Janghun Heo (Co-author, Ms, Ph.D integrated student) and Yong Taik Lim (Corresponding author, Sungkyunkwan Uni. Prof.)