A tumor-targeting nano-adjuvant for in situ vaccine based on ultrasound therapy

Ultrasound-generated antigens combined with TLR7/8 agonists as adjuvants have demonstrated significant anti-tumor efficacy as an in-situ vaccine. However, the use of TLR7/8 agonists can cause severe inflammatory responses. In this study, we present a novel tumor-targeting nano-adjuvant termed aPDL1-PLG/R848 NPs, which are composed of aPDL1 antibody, Fc-III-4C peptide linker (Fc-linker) and poly(L-glutamic acid)-grafted-R848. Under ultrasound irradiation, antigen-presenting cells activate immune mechanisms in vivo under dual stimulation of in situ antigens and immune adjuvants. The strategy inhibits primary tumor growth and induces a strong antigen-specific immune memory effect to prevent tumor recurrence in vivo. This work offers a safe and potent platform for an in situ cancer vaccine based on ultrasound therapy. Ultrasound therapy induces in situ vaccination (ISV) by promoting tumor immunogenic death, and the tumor-targeting nano-adjuvant (aPDL1-PLG/R848 NPs) enhances the ISV effect by tumor-targeted delivery of R848, minimizing side effects. This synergy triggers a robust systemic antitumor immune response for in situ cancer vaccination.image