“Cancer-treating-cancer” strategy: Entrapping engineered dying cancer cells in immunotherapeutic hydrogel against tumor recurrence

In this study, researchers developed a “cancer-treating-cancer” hydrogel therapy: engineered dying cancer cells embedded with the anticancer agent β-elemene are delivered into the surgical cavity, where the fibrin hydrogel traps residual tumor cells and provides sustained chemo-immunotherapy. The approach significantly suppressed postoperative relapse in preclinical models by combining local cytotoxicity with potent immune activation.

A key aspect of the work is the comprehensive proteomic analysis they applied to assess therapy effects. By coupling nanoparticle-enabled, MS-based proteomics with their biomaterials and immunotherapy system, the authors identified changes in protein expression tied to immune activation, macrophage polarization (M1/M2 balance), dendritic cell engagement, and cytotoxic T-cell cross-priming — shedding light on how the hydrogel reshapes the tumor microenvironment to suppress relapse.

The nanoparticle-enabled Proteograph^® workflow is uniquely suited for mechanistic studies like this because it can unbiasedly resolve thousands of proteins across complex biological systems, including those involving mixed cellular sources or animal models. Unlike targeted affinity assays, Proteograph data can capture low-abundance cytokines, matrix-remodeling enzymes, immune-response mediators, and unexpected pathway changes without prior assumptions, enabling clearer interpretation of mechanism of action, on-target and off-target effects, and potential biomarkers of treatment response or relapse. This makes deep Proteograph proteomics a powerful companion tool for evaluating next-generation biomaterial, cell-based, and combinatorial cancer therapies.