Extracellular Matrix Scaffold‐Assisted Tumor Vaccines Induce Tumor Regression and Long‐Term Immune Memory

• Published in: Advanced materials (Weinheim) Vol. 36; no. 15; pp. e2309843 - n/a
• Main Authors: Pal, Sanjay, Chaudhari, Rohan, Baurceanu, Iris, Hill, Brenna J., Nagy, Bethany A., Wolf, Matthew T.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.04.2024
• Subjects: Adjuvants; Antigens; biomaterials; Biomedical materials; Cancer; cancer immunotherapy; cancer vaccine; Cancer vaccines; Cytotoxicity; decellularized extracellular matrix; Effectiveness; Extracellular matrix; Healing; immunoengineering; Inflammatory response; Lymphocytes; Scaffolds; Tumors; Vaccines; decellularized extracellular matrix; biomaterials; immunoengineering; cancer vaccine; cancer immunotherapy
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.202309843

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 CD8+ cytotoxic 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. Injectable decellularized extracellular matrix (ECM) scaffolds enhance the efficacy of therapeutic cancer vaccines using tumor protein antigen and an immune‐stimulating STING agonist. ECM scaffolds prolong antigen release and recruit antigen‐presenting cells to help generate heightened cytotoxic T cell responses leading to effective tumor killing.