Gelatin/Hyaluronic Acid Scaffold Coupled to CpG and MAGE-A5 as a Treatment against Murine Melanoma.
Gabriela Piñón-ZárateBeatriz Hernández-TéllezKatia Jarquin-YanezMiguel Ángel Herrera-EnríquezAmérica Eréndira Fuerte-PérezEsther Alejandra Valencia-EscamillaAndrés Eliú Castell-RodríguezPublished in: Polymers (2022)
The half-time of cells and molecules used in immunotherapy is limited. Scaffolds-based immunotherapy against cancer may increase the half-life of the molecules and also support the migration and activation of leukocytes in situ. For this purpose, the use of gelatin (Ge)/hyaluronic acid (HA) scaffolds coupled to CpG and the tumor antigen MAGE-A5 is proposed. Ge and HA are components of the extracellular matrix that stimulate cell adhesion and activation of leucocytes; CpG can promote dendritic cell maturation, and MAGE-A5 a specific antitumor response. C57BL/6 mice were treated with Ge/HA/scaffolds coupled to MAGE-A5 and/or CpG and then challenged with the B16-F10 melanoma cell line. Survival, tumor growth rate and the immune response induced by the scaffolds were analyzed. Ge/HA/CpG and Ge/HA/MAGE-A5 mediated dendritic cell maturation and macrophage activation, increased survival, and decreased the tumor growth rate and a tumor parenchyma with abundant cell death areas and abundant tumor cells with melanin granules. Only the scaffolds coupled to MAGE-A5 induced the activation of CD8 T cells. In conclusion, Ge/HA scaffolds coupled to CpG or MAGE-A5, but not the mixture, can induce a successful immune response capable of promoting tumor cell clearance and increased survival.
Keyphrases
- hyaluronic acid
- tissue engineering
- dendritic cells
- dna methylation
- immune response
- extracellular matrix
- cell death
- cell adhesion
- regulatory t cells
- cell cycle arrest
- single cell
- oxidative stress
- stem cells
- type diabetes
- squamous cell carcinoma
- cell therapy
- metabolic syndrome
- inflammatory response
- stress induced
- bone marrow
- young adults
- combination therapy