HER2/neu is an immunogenic
protein inducing both humoral and cell-mediated immune responses. The
antigen-specific cytotoxic T lymphocytes (CTLs) are the main effector immune cells in the anti-
tumor immunity. To induce an effective CTL specific response against P5+435 single
peptide derived from rat HER2/neu oncogene, we used a
liposome delivery vehicle. In vivo enhancement of
liposome stability and intracytoplasmic delivery of
peptides are the main strategies which elevate the
liposome-mediated drug delivery.
Liposomes containing high transition temperature
phospholipids, such as DSPC, are stable with prolonged in vivo circulation and more accessibility to the immune system. Incorporation of DOPE
phospholipid results in the effective delivery of
peptide into the cytoplasm via the endocytotic pathway. To this end, the P5+435
peptide was linked to Maleimide-PEG2000-DSPE and coupled on the surface of nanoliposomes containing DSPC:
DSPG:
Cholesterol with/without DOPE. We observed that mice vaccinated with Lip-DOPE-P5+435 formulation had the highest number of IFN-γ- producing CTLs with the highest cytotoxic activity that consequently led to significantly smallest
tumor size and prolonged survival rate in the TUBO mice model. In conclusion, our study indicated that the liposomal form of P5+435
peptide containing DOPE can be regarded as a promising prophylactic anti-
cancer vaccine to generate potent
antigen-specific immunity.