Abstract
Injectable scaffold delivery is a strategy to enhance the efficacy of cancer vaccine immunotherapy. The choice of scaffold biomaterial is crucial, impacting both vaccine release kinetics and immune stimulation via the host response. Extracellular matrix (ECM) scaffolds prepared from decellularized tissues facilitate a pro-healing inflammatory response that promotes local cancer immune surveillance. Here, an ECM scaffold-assisted therapeutic cancer vaccine that maintains an immune microenvironment consistent with tissue reconstruction is engineered. Several immune-stimulating adjuvants are screened to develop a cancer vaccine formulated with decellularized small intestinal submucosa (SIS) ECM scaffold co-delivery. It is found that the STING pathway agonist cyclic di-AMP most effectively induces cytotoxic immunity in an ECM scaffold vaccine, without compromising key interleukin 4 (IL-4) mediated immune pathways associated with healing. ECM scaffold delivery enhances therapeutic vaccine efficacy, curing 50-75% of established E.G-7OVA lymphoma tumors in mice, while none are cured with soluble vaccine. SIS-ECM scaffold-assisted vaccination prolonged antigen exposure is dependent on CD8cytotoxic T cells and generates long-term antigen-specific immune memory for at least 10 months post-vaccination. This study shows that an ECM scaffold is a promising delivery vehicle to enhance cancer vaccine efficacy while being orthogonal to characteristics of pro-healing immune hallmarks.
Overview
- The study investigates the use of injectable scaffold delivery to enhance the efficacy of cancer vaccine immunotherapy. The choice of scaffold biomaterial is crucial, impacting both vaccine release kinetics and immune stimulation via the host response. The study engineers an ECM scaffold-assisted therapeutic cancer vaccine that maintains an immune microenvironment consistent with tissue reconstruction. Several immune-stimulating adjuvants are screened to develop a cancer vaccine formulated with decellularized small intestinal submucosa (SIS) ECM scaffold co-delivery. The study aims to answer the question of whether ECM scaffold delivery enhances therapeutic vaccine efficacy and generates long-term antigen-specific immune memory for at least 10 months post-vaccination.
Comparative Analysis & Findings
- The study compares the outcomes observed under different experimental conditions or interventions, specifically comparing the efficacy of a soluble vaccine versus an ECM scaffold-assisted vaccine. The results show that the ECM scaffold-assisted vaccine cures 50-75% of established E.G-7OVA lymphoma tumors in mice, while none are cured with soluble vaccine. The study identifies that the STING pathway agonist cyclic di-AMP most effectively induces cytotoxic immunity in an ECM scaffold vaccine, without compromising key interleukin 4 (IL-4) mediated immune pathways associated with healing. The study also finds that ECM scaffold delivery enhances therapeutic vaccine efficacy by prolonging antigen exposure, which is dependent on CD8cytotoxic T cells and generates long-term antigen-specific immune memory for at least 10 months post-vaccination.
Implications and Future Directions
- The study's findings have significant implications for the field of research and clinical practice, as they demonstrate the potential of ECM scaffold delivery to enhance cancer vaccine efficacy. The study identifies that an ECM scaffold is a promising delivery vehicle to enhance cancer vaccine efficacy while being orthogonal to characteristics of pro-healing immune hallmarks. The study suggests future research directions that could build on the results of the study, explore unresolved questions, or utilize novel approaches. For example, future studies could investigate the use of other ECM scaffolds or adjuvants to enhance cancer vaccine efficacy, or explore the potential of ECM scaffold delivery in combination with other immunotherapies.