Vaccination with
heat shock proteins (HSP) protects mice from challenge with the
tumor from which the HSP were isolated. The antigenicity of HSP vaccination is thought to result from HSP-associated endogenous major histocompatibility complex class I
peptides or their precursors. The vaccination effect can be achieved in an adjuvant-free manner and is mediated by CD8(+) T cells, indicating that HSP can act as a natural adjuvant and cross-prime T cells in vivo. We previously devised a
recombinant vaccine composed of a CD8(+)
T cell epitope fused to the carboxyl-terminus of hsc70 and demonstrated efficient generation of
antigen-specific cytotoxic T lymphocyte (CTL) after vaccination with a few micrograms of the hsc70-CTL
epitope fusion
protein. The present study aimed to determine if the fusion
protein vaccine could control
tumor growth in vivo and whether simultaneous fusion of a CD4(+)
T cell epitope to the amino terminus of the hsc70-CTL
epitope would be a more potent
vaccine compared to the CTL
epitope alone.
Ovalbumin (OVA)-derived 8 mer
peptide, OVA(257-264), and 16mer
peptide, OVA(265-280), were used as CD8(+) and CD4(+)
T cell epitopes, respectively. Vaccination with hsc70-OVA(257-264) generated
peptide specific CTL more effectively than a
peptide plus
incomplete Freund's adjuvant combination, and suppressed growth of OVA expressing EL4 (E.G7) and
B16 melanoma tumor cells. Addition of OVA(265-280) to the amino-terminus of hsc70-OVA(257-264) (OVA(265-280)-hsc70-OVA(257-264)) enhanced the generation of the OVA(257-264)-specific CTL population, leading to better eradication of MO5 lung
metastasis compared to hsc70-OVA(257-264). Our results suggest that fusion of both CD4(+) and CD8(+)
T cell epitopes to hsc70 enhances
tumor immunity beyond the effect of the CD8(+)
T cell epitope alone.