Abstract
Rationale: Tumor cells are ideal candidates for developing cancer vaccines due to their antigenic profiles, yet existing whole-cell vaccines lack efficacy. This study aimed to develop a novel whole-cell vaccine platform that combines immunogenicity, structural integrity, and tumor-targeting capabilities. Methods: We created "Magnetic Sculpture-like (MASK) Cells" by treating tumor cells with high-concentration FeCl3, inducing rapid morphological fixation without traditional chemical crosslinking. MASK cells were characterized for proliferative capacity, biomolecule retention, and magnetic properties. Vaccine efficacy was tested in vitro, in melanoma-bearing mouse models, and through spatial transcriptomic profiling of tumor microenvironments. Combination therapy with anti-PD-1 was further evaluated. Results: MASK cells lose proliferative ability but retain biomolecules and architecture. MASK cells promote dendritic cell maturation and T cell responses against tumors. Vaccines combining MASK cells and adjuvant potently suppress melanoma growth. Uniquely, FeCl3 sculpting imparts magnetism to cells, enabling directional navigation to tumors using magnetic fields and enhanced in situ immune activation. Spatial transcriptomics reveals DC and T cell activation and tumor cytotoxicity after MASK vaccination. Combined with anti-PD-1, MASK cell vaccines strongly inhibit growth and improve survival. Conclusion: MASK cells represent a promising new approach for targeted, patient-specific anti-tumor therapeutics.