Professor Yong Taek Lim's research team at the Sungkyunkwan Advanced Institute of Nano Technology (SAINT) has developed a next-generation cancer immunotherapy inspired by the antiviral immune responses triggered during infection. The study mimics the dynamic behavior of pathogens, leveraging the synergistic effects of sequential Toll-like receptor (TLR) signaling and the self-replication-driven sustained immune response observed in pathogens. This innovative approach significantly enhances the efficacy of traditional immunotherapies.

The findings were published online in two renowned journals in the fields of nanobiotechnology and materials science: Advanced Materials (IF=27.4) on October 9, 2024, and Advanced Functional Materials (IF=18.5) on November 3, 2024.

Bioadhesive Immune Niche Domain (BIND) to overcome the limitations of conventional Toll-like receptor 7/8 agonist-based therapies. Utilizing bioadhesive tannic acid, BIND is designed to adhere to and penetrate lymph nodes, enabling localized and sustained immune activation. This vaccine mimics the kinetics of pathogen self-replication, allowing gradual and sustained antigen delivery within lymph nodes for 7–14 days. Moreover, it replicates the viral mechanism of lymph node penetration by leveraging collagen interactions to efficiently infiltrate lymph nodes and induce the effective generation of antigen-specific T cells. In melanoma models, this vaccine demonstrated significantly higher anticancer efficacy than traditional mRNA-based cancer vaccines.

Professor Lim’s team also addressed the side effects of the BCG vaccine, commonly used for pediatric tuberculosis and bladder cancer. Despite its widespread use, the BCG vaccine is often associated with adverse effects like inflammation and secondary infections, as well as limited long-term efficacy. To overcome these issues, the team extracted a cell-wall skeleton capable of stimulating Toll-like receptor 2 (TLR-2) from the Microbacterium strain. They formulated this component with a TLR-7/8 agonist (t-TLR-7/8a) to create a "Reconstituted Synthetic Nanopathogen (RSnP)."

The RSnP showed remarkable therapeutic efficacy in bladder cancer models, even when used alone. When combined with the Treg-depleting anti-CCR8 antibody, it demonstrated exceptional results, achieving complete remission in large, previously difficult-to-treat tumors. Furthermore, systemic toxicity analysis revealed that RSnP exhibited low toxicity comparable to the control group, highlighting its potential for clinical application as a virulence-free treatment option.

Research article: Transformable Gel-to-Nanovaccine Enhances Cancer Immunotherapy via Metronomic-Like Immunomodulation and Collagen-Mediated Paracortex Delivery (Advanced Materials; IF=27.4, Oct 09, 2024)

Author: Seung Mo Jin (First author, Post-doctoral researcher), Ju Hee Cho (Co-author, Researcher), Yejin Gwak (Co-author, PhD-MS student), Sei Hyun Park (Co-author, PhD student), Jin-Ho Choi (Co-author, PhD student), Hong Sik Shin (Co-author, PhD student), Yong Taik Lim (Corresponding author, SKKU professor)

Research article: Virulence-Free Reconstituted Synthetic Nanopathogen Empowered by Timely-Activating TLR Agonist Promotes Heterologous Cancer Immunotherapy with Depletion of Tumor-Specific Treg Cells (Advanced Functional Materials; IF=18.5, Nov 03, 2024)

Author: Sang Nam Lee (First author, Post-doctoral researcher), Sei Hyun Park (Co-author, PhD student), Jin-Ho Choi (Co-author, PhD student), Jang Hun Heo (Co-author, PhD-MS student), Yong Taik Lim (Corresponding author, SKKU professor)