Journal for immunotherapy of cancer · 2025
Implantable artificial lymph node enables rapid in vivo neoantigen-specific T-cell generation and expansion for improving antitumor immunity.
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Cai Zhixiong, Lin Kongying, Dong Xiuqing, Li Zhenli, Chen Geng, Guo Luobin, Mou Pan, Chen Peizhe, Huang Junjing, Li Ling, Liu Xiaolong, Tang Ruijing, Zeng Yongyi
Аннотация
BACKGROUND: Tumor neoantigen vaccines typically require multiple prime-boost immunizations over several weeks or even months to elicit sufficient neoantigen-specific T-cell responses, which greatly limits their effectiveness against rapidly progressing cancers, such as hepatocellular carcinoma.
METHODS: Here, we developed a functionalized alginate scaffold for T-cell activation as an artificial lymph node (FAST-LN) to rapidly and efficiently generate tumor neoantigen-specific T cells in vivo. The FAST-LN consists of an alginate scaffold crosslinked with calcium ions and hyaluronic acids conjugated with anti-TIM-3 (T cell immunoglobulin and mucin domain-containing protein-3) antibodies, then incorporates tumor neoantigen-encoding adenoviral vaccines, dendritic cells (DCs), and various cytokines (C-C motif chemokine ligand 21 (CCL21), interleukin (IL)-2, IL-4, and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)) that maintain DC maturation and recruit T cells for antigen presentation.
RESULTS: This design facilitates efficient DC-T cell interactions within FAST-LN, enabling rapid generation of neoantigen-specific T cells for antitumor responses. In vivo antitumor studies demonstrated superior therapeutic efficacy of FAST-LN over traditional vaccines in mouse tumor models. Mechanistically, FAST-LN significantly enhanced tumor infiltration of CD8+ T cells, Th1 cells and macrophages, orchestrating robust antitumor responses.
CONCLUSIONS: Our results demonstrate that implantable FAST-LN rapidly induces tumor neoantigen-specific T cells in vivo, offering a promising strategy for neoantigen-based cancer immunotherapy.
METHODS: Here, we developed a functionalized alginate scaffold for T-cell activation as an artificial lymph node (FAST-LN) to rapidly and efficiently generate tumor neoantigen-specific T cells in vivo. The FAST-LN consists of an alginate scaffold crosslinked with calcium ions and hyaluronic acids conjugated with anti-TIM-3 (T cell immunoglobulin and mucin domain-containing protein-3) antibodies, then incorporates tumor neoantigen-encoding adenoviral vaccines, dendritic cells (DCs), and various cytokines (C-C motif chemokine ligand 21 (CCL21), interleukin (IL)-2, IL-4, and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)) that maintain DC maturation and recruit T cells for antigen presentation.
RESULTS: This design facilitates efficient DC-T cell interactions within FAST-LN, enabling rapid generation of neoantigen-specific T cells for antitumor responses. In vivo antitumor studies demonstrated superior therapeutic efficacy of FAST-LN over traditional vaccines in mouse tumor models. Mechanistically, FAST-LN significantly enhanced tumor infiltration of CD8+ T cells, Th1 cells and macrophages, orchestrating robust antitumor responses.
CONCLUSIONS: Our results demonstrate that implantable FAST-LN rapidly induces tumor neoantigen-specific T cells in vivo, offering a promising strategy for neoantigen-based cancer immunotherapy.