An Outer Membrane Vesicle-Based Vaccine Combined with alb-Flt3L Promotes Durable Antitumor Immunity in HPV-Associated...

Background/Objectives: Human papillomavirus (HPV)-associated cancers remain a major global health burden, and no therapeutic cancer vaccine has yet been approved. Oncoprotein E7 plays a key role in tumor initiation and progression and has been identified as a potential target. Here, we aim to improve the efficacy and durability of an outer membrane vesicle (OMV)-based E7-targeted vaccine, SOMV-9RE7, through alb-Flt3L combination therapy. Methods: The antitumor efficacy and durability of the combination therapy were evaluated in low-burden and high-burden HPV-positive TC-1 tumor-bearing mouse models. Systemic and local immune responses were investigated by flow cytometry. Results: Combination with alb-Flt3L improved the tumor control and prolonged the therapeutic durability of SOMV-9RE7 compared with monotherapy groups, with more than half of the treated mice surviving beyond 60 days. This combination strategy enhanced E7-specific CD8⁺ T cell immunity in peripheral blood and the spleen, reduced myeloid-derived suppressor cell (MDSC)-mediated immunosuppression, promoted splenic T cell memory formation, and reshaped the tumor microenvironment. Conclusions: Combining vaccine SOMV-9RE7 with alb-Flt3L improves antitumor efficacy and durability. This therapeutic benefit is associated with both systemic and local immune remodeling, supporting the combination therapy as a promising strategy for therapeutic cancer vaccines.