Resiquimod‐Induced Nanovaccine (RINV) for Personalized Cancer Immunotherapy

Abstract

Abstract Cancer nanovaccines have emerged as a promising modality for cancer immunotherapy due to their capability of eliciting robust tumor‐specific immune responses. However, structural complexity and insufficient spatiotemporal coordination of immune activation pose substantial challenges for optimizing the therapeutic potential of nanovaccines. Herein, a resiquimod‐induced nanovaccine (RINV) is devised for personalized cancer immunotherapy. Toll‐like receptor (TLR) 7/8 agonist resiquimod (R848) was covalently conjugated to fifth‐generation polyamidoamine (G5‐PAMAM) dendrimer through a disulfide linker to obtain the vaccine carrier G5‐R848. In this design, R848 not only fulfills its biological role as a vaccine adjuvant but facilitates uniform nanovaccine formation with the model protein antigen ovalbumin (OVA) due to its distinctive chemical structure. Redox‐triggered intracellular R848 release further promotes cytosolic delivery of antigen and subsequent antigen cross‐presentation. In vivo studies demonstrated that the nanovaccine induces remarkable prophylactic and therapeutic effects in the B16F10‐OVA melanoma model. Moreover, G5‐R848 forms personalized nanovaccines by complexing with cell lysates from resected B16F10 and 4T1 tumor tissues, effectively inhibiting postoperative tumor recurrence and metastasis.