Extracellular Matrix Scaffold-Assisted Tumor Vaccines Induce Tumor Regression and Long-Term Immune Memory,Advanced Materials

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Extracellular Matrix Scaffold-Assisted Tumor Vaccines Induce Tumor Regression and Long-Term Immune Memory
Advanced Materials ( IF 27.4 ) Pub Date : 2024-02-01 , DOI: 10.1002/adma.202309843
Sanjay Pal ₁ , Rohan Chaudhari _{1,

2} , Iris Baurceanu ₁ , Brenna J Hill ₃ , Bethany A Nagy ₄ , Matthew T Wolf ₁

Affiliation

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.

中文翻译：

细胞外基质支架辅助肿瘤疫苗诱导肿瘤消退和长期免疫记忆

可注射支架递送是增强癌症疫苗免疫治疗功效的一种策略。支架生物材料的选择至关重要，它会影响疫苗释放动力学和通过宿主反应进行的免疫刺激。由脱细胞组织制备的细胞外基质（ECM）支架可促进促愈合炎症反应，从而促进局部癌症免疫监视。在这里，设计了一种 ECM 支架辅助的治疗性癌症疫苗，可维持与组织重建一致的免疫微环境。筛选了几种免疫刺激佐剂，以开发一种由脱细胞小肠粘膜下层 (SIS) ECM 支架共同递送配制而成的癌症疫苗。研究发现，STING 通路激动剂环二-AMP 在 ECM 支架疫苗中最有效地诱导细胞毒性免疫，而不会损害与愈合相关的关键白细胞介素 4 (IL-4) 介导的免疫通路。 ECM 支架递送增强了治疗性疫苗的功效，治愈了小鼠体内 50-75% 已建立的 EG-7OVA 淋巴瘤肿瘤，而可溶性疫苗则无法治愈。 SIS-ECM支架辅助疫苗接种延长的抗原暴露依赖于CD8 ⁺细胞毒性T细胞，并在疫苗接种后产生至少10个月的长期抗原特异性免疫记忆。这项研究表明，ECM 支架是一种有前途的递送工具，可以增强癌症疫苗的功效，同时与促愈合免疫标志的特征正交。

更新日期：2024-02-01

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