Journal: bioRxiv

Article Title: A Transient Immunostimulatory Niche Synergizes Adoptive and Endogenous Immunity for Enhanced Tumor Control

doi: 10.1101/2025.08.22.671875

Figure Lengend Snippet: ( A ) Schematic illustration demonstrating proposed mechanism of ACTIVATE: (i-ii) Injected hydrogel containing adoptive T cells and cytokine(s) enables long-term local retention of cytokine alongside sustained adoptive T cell expansion and release over the course of 2 weeks; (iii) recruitment of endogenous immune cells, generating a local inflammatory niche for activation and expansion of endogenous immune cells; (iv) adoptive T cell and cytokine release elicit potent tumor cell killing, releasing antigens that can be (v) picked up by antigen-presenting cells and taken back to the tumor-draining lymph nodes for (vi) cross-presentation to endogenous T cells; (vii) combined with the activation and differentiation of endogenous immune cells in the tumor- draining lymph nodes provoked by drainage of adoptive T cells and cytokine enable (viii) engagement of endogenous immune cells for enhanced anti-tumor efficacy. ( B ) Polymer- nanoparticle hydrogels formed through self-assembly of dodecyl-modified hydroxypropyl methylcellulose (HPMC-C12) and degradable PEG-PLA core-shell nanoparticles, enabling co- encapsulation of adoptive T cells and stimulatory cytokines.

Article Snippet: Human cytokines were purchased from R&D Systems (Recombinant IL-2 Protein, Recombinant IL-7 Protein, Recombinant IL-2 Protein, Recombinant IL-15 Protein) and murine cytokines were purchased from Sino Biological (IL-2, IL-7, and IL-12A & IL-12B Heterodimer Protein (His Tag)) and PeproTech (Recombinant murine IL-15).

Techniques: Injection, Activation Assay, Polymer, Modification, Encapsulation

Journal: bioRxiv

Article Title: A Transient Immunostimulatory Niche Synergizes Adoptive and Endogenous Immunity for Enhanced Tumor Control

doi: 10.1101/2025.08.22.671875

Figure Lengend Snippet: ( A ) Schematic of in vitro release assay of cytokines from ACTIVATE immersed in PBS. ( B ) %Mass of cytokines IL-12, IL-7, IL-2, and IL-15 released and remaining in the hydrogels over the 1-week assay. ( C ) Schematic of in vitro cellular release assay: Hydrogel containing PMEL adoptive T cells and cytokine is injected into a porous transwell suspended over medium. Cells proliferate within the hydrogel while also releasing into the medium below. At each timepoint, the medium below the transwell is collected, cells are counted, and transwell is placed into fresh media. ( D ) Cumulative number of cells released into the medium over various timepoints for PMEL and cytokine encapsulated hydrogels and PMEL only control. ( E ) Total number of cells remaining in ACTIVATE on the final day of the assay. ( F ) Total cell exposure determined as the sum of cumulative cells released and total cells remaining in the hydrogel on day 8. ( G ) Cell viability of the cells remaining in the hydrogels on the final day of the assay. ( H ) Representative flow cytometry plots and quantification of PD-1 MFI of PMEL cells in the gel 3 days after encapsulation. ( I ) Frequency of central memory (CD62L + CD44 + ) and effector memory (CD62L - CD44 + ) phenotypes for PMEL cells in the hydrogel 3 days after co-encapsulation with different cytokines. Data are representative of n = 3 technical replicates per group and presented as mean ± s.e.m. P values were determined by ordinary one-way ANOVA followed by Tukey’s multiple comparison test using GraphPad PRISM.

Article Snippet: Human cytokines were purchased from R&D Systems (Recombinant IL-2 Protein, Recombinant IL-7 Protein, Recombinant IL-2 Protein, Recombinant IL-15 Protein) and murine cytokines were purchased from Sino Biological (IL-2, IL-7, and IL-12A & IL-12B Heterodimer Protein (His Tag)) and PeproTech (Recombinant murine IL-15).

Techniques: In Vitro, Release Assay, Injection, Control, Flow Cytometry, Encapsulation, Comparison