Use of tumor-associated antigens
for cancer immunotherapy is limited
due to their poor in vivo stability and low cellular
uptake. Delivery of antigenic peptides using synthetic polymer-based
nanostructures has been actively pursued but with limited success.
Peptide-based nanostructures hold much promise as delivery vehicles
due to their easy design and synthesis and inherent biocompatibility.
Here, we report self-assembly of a dipeptide containing a non-natural
amino acid, α,β-dehydrophenylalanine (ΔF), into
nanotubes, which efficiently entrapped a MAGE-3-derived peptide (M3).
M3 entrapped in F-ΔF nanotubes was more stable to a nonspecific
protease treatment and both F-ΔF and F-ΔF-M3 showed no
cellular toxicity for four cancerous and noncancerous cell lines used.
F-ΔF-M3 showed significantly higher cellular uptake in RAW 267.4
macrophage cells compared to M3 alone and also induced in
vitro maturation of dendritic cells (DCs). Immunization of
mice with F-ΔF-M3 selected a higher number of IFN-γ secreting
CD8+ T cells and CD4+ T compared to M3 alone.
On day 21, a tumor growth inhibition ratio (TGI, %) of 41% was observed
in a murine melanoma model. These results indicate that F-ΔF
nanotubes are highly biocompatible, efficiently delivered M3 to generate
cytotoxic T lymphocytes responses, and able to protect M3 from degradation
under in vivo conditions. The F-ΔF dipeptide-based
nanotubes may be considered as a good platform for further development
as delivery agents.