Personalized 3D Vaccine Integrates Immunotherapy and Antiangiogenic Therapy to Prevent Oral Squamous Cell Carcinoma Recurrence

Abstract The immune‐suppressive microenvironment and extensive tumor angiogenesis are key contributors to the high recurrence and mortality rates of oral squamous cell carcinoma (OSCC). To address these challenges, a personalized 3D‐printed anti‐tumor vaccine (3D‐Vax‐L) is developed that integrates whole tumor antigens from postoperative tissue lysates with the angiogenesis inhibitor, lenvatinib. This vaccine not only possesses inherent adjuvant properties but also mimics the functions of lymph nodes through its porous structure, facilitating the recruitment and maturation of immune cells. In vivo studies in OSCC animal models, including mice and rabbits, demonstrate that 3D‐Vax‐L effectively recruits and matures immune cells at postoperative sites, inhibits angiogenesis and tumor recurrence, and extends survival time, all while maintaining a stable morphology and an excellent biosafety. Furthermore, 3D‐Vax‐L supports facial integrity post‐surgery, addressing physical challenges by preventing collapse and reducing the risk of aesthetic‐related disorders. These findings suggest that 3D‐Vax‐L is a promising therapeutic technique for preventing post‐surgical OSCC relapse, particularly as it offers a new strategy for immune system activation and demonstrates significant potential for clinical translation.