[HTML][HTML] Vaccination with EphA2-derived T cell-epitopes promotes immunity against both EphA2-expressing and EphA2-negative tumors

M Hatano, N Kuwashima, T Tatsumi, JE Dusak… - Journal of translational …, 2004 - Springer
M Hatano, N Kuwashima, T Tatsumi, JE Dusak, F Nishimura, KM Reilly, WJ Storkus
Journal of translational medicine, 2004Springer
Background A novel tyrosine kinase receptor EphA2 is expressed at high levels in advanced
and metastatic cancers. We examined whether vaccinations with synthetic mouse EphA2
(mEphA2)-derived peptides that serve as T cell epitopes could induce protective and
therapeutic anti-tumor immunity. Methods C57BL/6 mice received subcutaneous (sc)
vaccinations with bone marrow-derived dendritic cells (DCs) pulsed with synthetic peptides
recognized by CD8+ (mEphA2 671–679, mEphA2 682–689) and CD4+ (mEphA2 30–44) T …
Background
A novel tyrosine kinase receptor EphA2 is expressed at high levels in advanced and metastatic cancers. We examined whether vaccinations with synthetic mouse EphA2 (mEphA2)-derived peptides that serve as T cell epitopes could induce protective and therapeutic anti-tumor immunity.
Methods
C57BL/6 mice received subcutaneous (s.c.) vaccinations with bone marrow-derived dendritic cells (DCs) pulsed with synthetic peptides recognized by CD8+ (mEphA2671–679, mEphA2682–689) and CD4+ (mEphA230–44) T cells. Splenocytes (SPCs) were harvested from primed mice to assess the induction of cytotoxic T lymphocyte (CTL) responses against syngeneic glioma, sarcoma and melanoma cell lines. The ability of these vaccines to prevent or treat tumor (s.c. injected MCA205 sarcoma or B16 melanoma; i.v. injected B16-BL6) establishment/progression was then assessed.
Results
Immunization of C57BL/6 mice with mEphA2-derived peptides induced specific CTL responses in SPCs. Vaccination with mEPhA2 peptides, but not control ovalbumin (OVA) peptides, prevented the establishment or prevented the growth of EphA2+ or EphA2-negative syngeneic tumors in both s.c. and lung metastasis models.
Conclusions
These data indicate that mEphA2 can serve as an attractive target against which to direct anti-tumor immunity. The ability of mEphA2 vaccines to impact EphA2-negative tumors such as the B16 melanoma may suggest that such beneficial immunity may be directed against alternative EphA2+ target cells, such as the tumor-associated vascular endothelial cells.
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