Fig. 1: Synthesizing and characterizing SIVETs. | Nature Communications

Fig. 1: Synthesizing and characterizing SIVETs.

From: Adoptive T cell transfer and host antigen-presenting cell recruitment with cryogel scaffolds promotes long-term protection against solid tumors

Fig. 1

a Schematic detailing the proposed mechanism of action. Step 1: Depots infused with T cells and loaded with factors that recruit antigen-presenting cells (APC) are injected adjacent to a tumor. Depots concurrently release T cells to debulk the tumor while recruiting APCs to the tumor site, where they become activated and process tumor antigen. Step 2: Tumor-antigen presenting APCs migrate to lymph nodes and prime host naïve, antigen-specific T cells. Step 3: Primed tumor-reactive host T cells traffic to the tumor, which is undergoing tumor debulking by the adoptively transferred T cells, and facilitate tumor rejection and long-term anti-tumor immunity. b Schematic of SIVET fabrication. Alginate and collagen type 1 are modified with tetrazine and norbornene respectively, and then reacted under cryogelation conditions (−12C to −18C) to form macroporous alginate-collagen hybrid cryogels. c Photographs of rod-shaped cryogels showing tunable lengths (left) and flexibility (right). d SEM image of cryogel showing macroporous structure. Image is representative of 8 SEM images from two cryogels. e SHG demonstrating pristine cryogel architecture and pore-size distribution. f Quantification of pore-size distribution from SHG represented as a violin plot. Data show the distribution of 150 pores. Boxplot information: minima = 1.6, maxima = 271.6, lower bound = 1.6, upper bound = 182.9, 25th percentile = 18.04, center = 42.19, 75th percentile = 88.83. g Tunable release of immunomodulatory factors from cryogels: CpG with or without PEI condensation (top left), IL2 and GM-CSF with or without pre-adsorption onto laponite (top right and bottom respectively). p-values for g–i was determined by two-way ANOVA with repeated measures. Data are mean ± s.d. from n = 3 for CpG and GMCSF, and n = 2 for IL2. h–j Analysis of local T cell persistence in vivo. h Schematic of the experimental set-up. CD8+ T cells were isolated from spleens of luciferase-expressing mice, activated in vitro, and either directly injected subcutaneously or loaded into depots before injection. i Bioluminescence images of administered T cells over time. j Quantification of T cell luciferase expression over time. p-value was determined by two-way ANOVA with repeated measures. Data are mean ± s.d. from n = 4.

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