Therapeutic Adoptive Cell Transfer (ACT) Vaccine Patch: Bioengineered Tumor Cells Prime Macrophage Immunoregulation to Prevent Postsurgical Tumor Recurrence and Metastasis

Abstract Incomplete surgical resection of solid tumors frequently leads to recurrence and metastasis, driving cancer mortality. While adoptive cell transfer (ACT) of tumor‐infiltrating lymphocytes (TILs) shows promise in preventing recurrence, its clinical adoption is hindered by lengthy manufacturing times and variable efficacy. Here, this work presents ACT‐vac, a rapidly producible personalized cancer vaccine that combines bacterially transfected autologous tumor cells with L ‐arginine‐mediated nitric oxide (NO) generation to combat postsurgical tumor recurrence and metastasis. This approach drives three synergistic mechanisms: (1) amplification of tumor‐specific antigen presentation; (2) reprogramming of tumor‐associated macrophages (TAMs) from an immune‐suppressive M2 to an immunogenic M1 phenotype via NF‐κB pathway activation; and (3) NO‐triggered tumor cell pyroptosis that releases additional immunogenic signals. When delivered via dissolving microneedle patches to a murine model of incompletely resected melanoma, ACT‐vac elicits marked suppression in tumor recurrence and metastasis. Notably, unlike traditional ACT therapies requiring 6–8 weeks of cell expansion, ACT‐vac can be produced within 72 h post‐resection. This rapid, personalized approach initiates a self‐amplifying immunologic cascade via macrophage‐centric immune remodeling, positioning it as a transformative strategy for preventing post‐surgical tumor recurrence and metastasis.