Extracellular Matrix Scaffold-Assisted Tumor Vaccines Induce Tumor Regression And Long-Term Immune Memory

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, we engineered an ECM scaffold-assisted therapeutic cancer vaccine that maintained an immune microenvironment consistent with tissue reconstruction. Several immune-stimulating adjuvants were screened to develop a cancer vaccine formulated with decellularized small intestinal submucosa ECM scaffold co-delivery. We found that the STING pathway agonist CDA most effectively induced cytotoxic immunity in an ECM scaffold vaccine, without compromising key IL-4 mediated immune pathways associated with healing. ECM scaffold delivery enhanced therapeutic vaccine efficacy, curing 50-75% of established EG.7 lymphoma tumors in mice, while none were cured with soluble vaccine. SIS-ECM scaffold-assisted vaccination prolonged antigen exposure, was dependent on CD8+ cytotoxic T cells, and generated 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. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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