Efficient Eradication of Established Tumors in Mice with Cationic Liposome-Based Synthetic Long-Peptide Vaccines

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 <i>in vivo</i> 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. <i>Cancer Immunol Res; 5(3); 222-33. ©2017 AACR</i>.