2024 World Conference on Lung Cancer (WCLC) - Posters-P1.03D.02 An Enhanced Immunotherapeutic Strategie for NSCLC via in Situ Tumor Nanovaccines and Activation of STING and TLR7/8 Pathways

P1.03D.02 An Enhanced Immunotherapeutic Strategie for NSCLC via in Situ Tumor Nanovaccines and Activation of STING and TLR7/8 Pathways

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This study highlights the development of an innovative in situ nanovaccine aimed at enhancing lung cancer immunotherapy by activating the STING and TLR7/8 pathways. This approach utilizes the body's immune system, particularly focusing on the role of dendritic cells (DCs), to target tumors more effectively than traditional methods like chemotherapy or radiotherapy. The novel nanovaccine, named PAEMA-PCR848, is designed to disintegrate in the acidic tumor environment and, upon activation by a 660 nm laser, induces photodynamic therapy. This process releases tumor-associated antigens (TAAs) and damage-associated molecular patterns, essential for converting tumors into sources of personalized antigens for vaccine development.<br /><br />The nanovaccine system comprises PEG-modified photosensitizer (PEG-Ce6), a tumor acid-responsive core (PAEMA), and an immune adjuvant (R848). This combination allows for a four-step cascade designed to enhance the body's immune response. The cascade includes PEG-Ce6's interaction with cell membranes to induce cell death and PAEMA's role in attractively delivering adjuvants and antigens to lymph nodes. There, dendritic cells uptake antigens, promoting DC maturation and activating cytotoxic CD8 T cells, leading to a robust antigen-specific anti-tumor immune response.<br /><br />In mouse models, this nanovaccine proved effective in inhibiting tumor growth and generating long-term immune memory, thus potentially reducing the recurrence and metastasis of tumors. The study's outcomes suggest a promising advancement in personalized cancer immunotherapy, optimizing immune activation and targeting mechanisms within tumors to improve therapeutic efficacy. The research was supported by the Natural Science Foundation of Guangdong, illustrating strong scientific collaboration in developing cutting-edge cancer therapies.

Asset Subtitle

Shaowei Wu

Meta Tag

Speaker Shaowei Wu

Topic Tumor Biology – Translational Biology

Keywords

nanovaccine

lung cancer

immunotherapy

STING pathway

TLR7/8 pathway

dendritic cells

PAEMA-PCR848

photodynamic therapy

tumor-associated antigens

personalized cancer therapy