Abstract 5761: A nanoplatform based on an in situ tumor vaccine and activation of STING and TLR7/8 pathways for enhanced NSCLC immunotherapy

Abstract Background: Immunotherapy has emerged as a promising treatment for tumors following surgical, radiotherapy, and chemotherapy interventions. Therapeutic tumor vaccines are considered highly effective in eliminating tumors and preventing their recurrence and metastasis due to their ability to induce or enhance T cell-mediated immune responses. However, the therapeutic efficacy of these vaccines is impeded by the heterogeneity present both between and within tumors. In contrast, in situ tumor vaccines, prepared from autologous antigens in tumor patients, present another promising strategy for generating comprehensive immune responses. Methods: In this study, we designed a multifunctional nanopolymer, the transformable nanoassembly PEG-Ce6@PAEMA/R848. This assembly includes the photosensitizer polyethylene glycol-chlorin-e6 (PEG-Ce6), the tumor pH-sensitive polymer poly (2-azepane ethyl methacrylate) (PAEMA), and the immune adjuvant Resiquimod (R-848). The objective is to confirm the activation of bone marrow-derived dendritic cells (DCs) at the cellular level. Subsequently, we investigated the maturation of DCs in lymph nodes and tumor sites in vivo. Results: In the particle characterization process, successful synthesis of nanoparticles was achieved, along with the verification of their acid-responsive function and toxic effects. Furthermore, in vitro experiments demonstrated the activation of bone marrow-derived dendritic cells (DCs) (Figure 1). To further investigate the in vivo vaccine effects, C57BL/6 mice were euthanized, and lymph nodes were extracted to examine the accumulation of FITC-PAEMA. It can be observed that, due to the reduction in size of the particles in the tumor acidic environment, the immune adjuvant can easily enter the lymph nodes. Activation of the STING pathway in dendritic cells within the lymph nodes was detected through qPCR. The maturation of dendritic cells (DCs) in the lymph nodes was determined using flow cytometry (Figure 2). Conclusions: In this study, we developed a straightforward yet potent strategy focused on in situ tumor targeting. This approach effectively inhibits tumor growth while inducing immunogenic cell death and eliciting a systemic anti-tumor immune response against cancer cells. Additionally, we intend to validate the therapeutic efficacy of this strategy on metastatic and distal tumors in subsequent investigations. Citation Format: Haiyu Zhou, Hengliang Hou, Bin Xu, Yucheng Huang, Hongrui Qiu. A nanoplatform based on an in situ tumor vaccine and activation of STING and TLR7/8 pathways for enhanced NSCLC immunotherapy abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 5761.