Localized hydrogel depots for CAR-T cell therapy in solid tumors: materials design, cellular fitness and...

Chimeric antigen receptor T-cell (CAR-T) therapy is less effective in solid tumors than in selected hematologic malignancies because vascular, stromal, spatial, and immunosuppressive barriers restrict cell delivery and function. Local hydrogels and related biomaterials can convert a transient administration into a spatially organized depot, but their benefit depends on more than polymer identity. This review therefore combines a scenario-driven framework-depot versus bolus, intratumoral versus peritumoral placement, unresected versus postsurgical disease, and cell-loaded versus cell-free support-with a materials-centered analysis of formation, administration, time-dependent mechanics, architecture, degradation, biochemical presentation, and manufacturing. Direct evidence is distinguished from adjacent mechanistic evidence and design hypotheses. Across the available studies, the best-supported functions are improved delivered-cell recovery, regional persistence, controlled presentation of supportive cues, and enhanced antitumor activity in selected preclinical models. By contrast, universal material-property optima, clinically validated hydrogel-CAR-T products, and cryopreservation of a final cell-loaded depot have not been established. We define practical tests for gelation and device compatibility, productive egression, material-to-cell fitness, component attribution, and integrated-product safety. A materials-focused comparative table and a 30-study evidence map separate measured values from inferred mechanisms and identify where CAR-T cells were directly loaded, administered separately, manufactured in a matrix, or generated in situ. The resulting framework emphasizes that successful platforms must coordinate material behavior, CAR-T quality, anatomical placement, and clinical workflow rather than maximizing retention or chemical complexity alone.