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Tailoring functional nanomaterials for CNS gene therapy and cancer imm…

일자
2023.03.06 (월)
시간
17:00~18:15
연사
주계일 교수
장소
환경공학동 101호 강당
소속
이화여자대학교

제목: Tailoring functional nanomaterials for CNS gene therapy and cancer immunotherapy

내용: Although many different gene delivery vectors, including nanoparticles and recombinant viruses, have been developed for central nervous system (CNS) gene therapy, their practical use for clinical applications were limited due to inefficient gene delivery to CNS target cells, mainly caused by the poor penetration of vectors through blood-brain barrier (BBB). Among these vectors, adeno-associated virus (AAV) is a preferred gene delivery vector owing to its safety profile, long-lasting expression in non-dividing cells, and relatively low immunogenicity compared with other viral vectors. However, the gene transfer efficacy of AAV to CNS tissues after intravenous injection is at least an order magnitude lower than to liver, which poses a significant challenge in CNS gene therapy. Therefore, we aimed to develop novel AAV capsid variants with greater specificity to desired CNS tissues to enhance the gene transfer efficacy and minimize the unwanted transduction in other tissues including liver.

 Despite the great promise of immune checkpoint blockade (ICB) therapy for cancer treatment, the currently available options for ICB treatment pose major clinical challenges, including the risk of severe systemic auto-immune responses. Here, we developed a novel localized delivery platform, immuno-bioglue (imuGlue), which is inspired by the intrinsic underwater adhesion properties of marine mussels and can allow the optimal retention of anti-PD-L1 drugs at tumor sites and the on-demand release of drugs in response to the tumor microenvironment. Using a triple-negative breast cancer and melanoma models, we found that imuGlue could significantly enhance anti-tumor efficacy by eliciting a robust T cell-mediated immune response while reducing systemic toxicity by preventing the rapid diffusion of anti-PD-L1 drugs into the systemic circulation and other tissues. It was also demonstrated that imuGlue could be successfully utilized for combination therapy with other immunomodulatory drugs to enhance the anti-tumor efficacy of ICB-based immunotherapy, demonstrating its versatility as a new treatment option for cancer immunotherapy.