| 摘要: | The recruitment and activation of dendritic cells (DCs), which are essential for the initiation of potent cytotoxic immune responses, in the tumor microenvironment (TME) have been the prime goal of potent cancer vaccine design strategies. A notable obstacle in the field of cancer immunotherapy has been the creation of a vaccine that elicits sufficient immunogenicity, at the same time, depict enhanced elements of biocompatibility and biodegradability. Hydrogels have over the years been used in tissue engineering for they provide a superior extracellular matrix (ECM) mimic that allows cell growth and interaction as in the biological ECM.
Herein, we develop a gelatin-based nanoparticular vaccine-loaded hydrogel system (Gel-HPA@OVA-PEI-Fucoidan@GM-CSF) to recruit and activate DCs for the activation of cytotoxic T-lymphocytes. To enhance the maturation of DCs, cytokine GM-CSF was included in the vaccine. Additionally, for a stronger and more widely immunogenic stimulus, Fucoidan has been included in the vaccine design. Principally, C57BL/6 mice are challenged with EG7.OVA cells, which are a model for the tumor, and later the vaccine, which contains OVA, our model for the tumor-specific antigens (TSA). Organs, tumor tissues, and blood serum are evaluated for integrity and immunological function.
Preliminary success has been realized in the synthesis and characterization of the hydrogel nanocomposite system, which demonstrates reasonable biocompatibility, slow and sustained release property, and biodegradability of the material. The ability to recruit and activate DCs in situ has been demonstrated.
The Gel-HPA@OVA-PEI-Fucoidan@GM-CSF hydrogel nanocomposite vaccine is a potent vaccine that represents another immunotherapeutic potential for utilization in targeted cancer immunotherapeutic interventions. |
