Tumor vaccine is the use of tumor antigen to cause the body to create particular anti-tumor effect, activate the body’s own immune defense mechanism, and achieve the function of tumor therapy or prevention. Despite having a strong theoretical foundation, vaccine-based antineoplastic treatment has yet to produce good clinical results. Improving the immune activation efficiency of vaccines is one of the mainstream research topics in the field of tumor immunotherapy.
Wang Hai’s team from the National Nanoscience Center of the Chinese Academy of Sciences published a research paper entitled “Direct Presentation of Tumor-Associated Antigens to Induce Adaptive Immunity by Personalized Dendritic Cell-Mimicking Nanovaccines” in Advanced Materials, about a highly efficient nano-dendritic cell vaccine that can directly present major histocompatibility complex (MHC)-tumor antigen to T cells.
In this work, bone marrow-derived dendritic cells (BMDCs) isolated from mice and generated in vivo were co-incubated with tumor cell-bacterial fusion material in vitro while adjusting the stimulation settings, yielding a tailored dendritic cell vaccine including MHC- tumor antigen complex. The cell membrane carrying personalized MHC- tumor antigen complex and costimulatory factor (CD80/86) was coated on folate-iron self-assembled dendritic nanoparticles in this work to create a nano-dendritic cell vaccine that can directly activate T cells to generate particular tumor immune response.
Results show that the nano-dendritic cells present significant lymph node homing ability and induce specific cellular immunity, effectively inhibiting tumor growth and metastasis in vivo, and induce long-term immune protection of memory T cells. It is expected to be used in individualized tumor immunotherapy.
mRNA technology can synthesize specific tumor antigens through the protein synthesis system of human cells to induce immune response and specifically attack tumor cells. Therefore, mRNA tumor vaccine has become another important strategy of personalized immunotherapy.
Lipid nanoparticles (LNPs) are used as non-viral delivery carriers to deliver mRNA to the cytoplasm, but the current cryopreservation and transport of mRNA-LNPs vaccines hinder their clinical application.
The researchers employed a deformable hydrogel-LNPs system (HA-mRLNPs) to store mRNA vaccine at room temperature for persistent immunotherapy in vivo in order to optimize the thermal stability and persistence of mRNA-LNPs vaccine to immune system activation. In this study, a novel LNPs encapsulating tumor antigen mRNA and immune adjuvant was constructed using a highly efficient microfluidic chip, and a dynamic hyaluronic acid hydrogel was employed to control LNP migration and fusion to improve the storage period of mRNA vaccine at room temperature.
Furthermore, the hyaluronic acid chain is mobile under physiological conditions and cannot maintain a gel-like form permanently, allowing for controlled release of mRNA nano-vaccine and delivery to dendritic cells, where antigen-specific T lymphocytes can then destroy tumor cells. The function of the nano-vaccine remained unaltered when it was kept at room temperature for at least 14 days. This work demonstrated that an immunological hydrogel-LNPs system that is stable and durable can be exploited for effective tumor immunotherapy.