Advanced Materials: Wang Hai's team from the National Nano Center has made a new breakthrough in tumor nanovaccines

Tumor vaccine refers to the use of tumor antigens to induce the body to produce specific anti-tumor effects through active immunity, stimulate the body's own immune protection mechanism, and achieve the role of
treating tumors or preventing tumorigenesis.
Although vaccine-based anti-tumor therapy has a superior theoretical basis, it has not achieved satisfactory clinical treatment results
.
Among them, improving the immune stimulation efficiency of vaccines is one of the important research directions in the field of
tumor immunotherapy.

On October 11, 2022, the research team of Wang Hai of the National Center for Nanoscience of the Chinese Academy of Sciences published a report in the journal Advanced Materials entitled: Direct Presentation of Tumor-Associated Antigens to Induce Adaptive Immunity by Personalized Dendritic Cell-Mimicking Research paper
on Nanovaccines.

In this study, a nanodendritic cell vaccine
with high efficiency and direct delivery of major histocompatibility complex (MHC)-tumor antigens to T cells was constructed.

In this study, bone marrow-derived dendritic cells (BMDCs) extracted and induced from mice and tumor cell-bacterial fusion materials were co-incubated by controlling stimulation conditions in vitro, so as to obtain personalized dendritic cell vaccines
containing MHC-tumor antigen complexes.
In this study, cell membranes containing personalized MHC-tumor antigen complexes and co-stimulatory factors (CD80/86) will be extracted and coated on folate-iron self-assembled dendritic nanoparticles to construct nanodendritic cell vaccines
that can directly stimulate T cells to induce specific tumor immune responses.

The experimental results show that the nanodendritic cells exhibit significant lymph node homing ability and induce specific cellular immunity, effectively inhibit tumor growth and metastasis formation in vivo, and induce long-term immune protection of memory T cells, which is expected to be used in personalized tumor immunotherapy
.

a.
Schematic diagram of synthetic nano-DC vaccine; b-d, SEM and TEM characterization of dendritic nanoparticles; E-f, nanoparticle size distribution and charge characterization; G-i, protein charge, and pull-down assays verify that nano-DC vaccines carry related vaccine-presenting
protein complexes.

mRNA technology can synthesize specific tumor antigens through the protein synthesis system of human cells to induce immune response and specifically attack tumor cells, so mRNA tumor vaccines have become another important strategy
for personalized immunotherapy.

Lipid nanoparticles (LNPs) serve as non-viral delivery vectors to deliver mRNA to the cytoplasm, and the current ultra-low temperature storage and transport of mRNA-LNPs vaccines hinders their clinical application
.

On November 11, 2022, Hai Wang's research team published a research paper entitled: Stabilizing RNA Nanovaccines with Transformable Hyaluronan Dynamic Hydrogel for Durable Cancer Immunotherapy in the journal Advanced Functional Materials
。

In this study, a hydrogel-LNPs system (HA-mRLNPs) was developed that can efficiently deliver mRNA encoding tumor antigens to dendritic cells for antigen presentation, inducing antigen-specific CD8+ T cells to kill tumor cells
.
It can also be stored
at room temperature.
This study proves that stable and durable immunohydrogel-LNPs systems can be used for effective tumor immunotherapy
.

To improve the thermostability and durability of mRNA-LNPs vaccines for immune system stimulation, the research team used a deformable hydrogel-LNPs system (HA-mRLNPs) that stores mRNA vaccines at room temperature for in vivo durable immunotherapy
.
This study achieved encapsulation of novel LNPs encoding tumor antigen mRNA and immune adjuvants by constructing a highly mixed-efficiency microfluidic chip, followed by dynamic hyaluronic acid hydrogels that restricted the migration and fusion of LNPs to improve the storage time
of mRNA vaccines at room temperature.

In addition, hyaluronic acid chains are mobile under physiological conditions and cannot remain gelatinous permanently, so that mRNA nanovaccines can be released in a controlled manner and delivered to dendritic cells, which in turn induce antigen-specific T cells to kill tumor cells
.
After the nanovaccine is stored at room temperature for at least 14 days, its function remains unchanged
.
This study proves that stable and durable immunohydrogel-LNPs systems can be used for effective tumor immunotherapy
.

Schematic diagram of hydrogel-LNPs system preparation and tumor immunity in vivo

Paper Link:

https://doi.
org/10.
1002/adma.
202205950

https://doi.
org/10.
1002/adfm.
202204636