Cancer Immunology Research · 2017 · 77 citations · 27 references
MedicineImmunologyOncologyCancer ImmunologyDrug DeliveryImmunotherapyCancer ImmunotherapyCancer VaccinesLiposome-based DeliveryTherapeutic VaccinationTherapeutic VaccinesVaccine DeliveryCationic LiposomesCd4 Positive T CellsCd4 T Cell ActivationLiposomal Delivery SystemsLiposomal NanocarriersLiposomesSynthetic Long Peptide VaccinesSynthetic Long Peptides
Abstract Therapeutic vaccination with synthetic long peptides (SLP) can be clinically effective against HPV-induced premalignant lesions; however, their efficiency in established malignant lesions leaves room for improvement. Here, we report the high therapeutic potency of cationic liposomes loaded with well-defined tumor-specific SLPs and a TLR3 ligand as adjuvant. The cationic particles, with an average size of 160 nm, could strongly activate functional, antigen-specific CD8+ and CD4+ T cells and induced in vivo cytotoxicity against target cells after intradermal vaccination. At a low dose (1 nmol) of SLP, our liposomal formulations significantly controlled tumor outgrowth in two independent models (melanoma and HPV-induced tumors) and even cured 75%–100% of mice of their large established tumors. Cured mice were fully protected from a second challenge with an otherwise lethal dose of tumor cells, indicating the potential of liposomal SLP in the formulation of powerful vaccines for cancer immunotherapy. Cancer Immunol Res; 5(3); 222–33. ©2017 AACR.
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