title: Vaccination with EphA2-derived T cell-epitopes promotes immunity against both EphA2-expressing and EphA2-negative tumors.
abstract: 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.
authors.affiliation: Department of Neurological Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA, 15213, USA. okadah@upmc.edu.
authors.forename: Manabu
authors.initials: M
authors.lastname: Hatano
authors.forename: Naruo
authors.initials: N
authors.lastname: Kuwashima
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tatsumi
authors.forename: Jill E
authors.initials: JE
authors.lastname: Dusak
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Nishimura
authors.forename: Karlyne M
authors.initials: KM
authors.lastname: Reilly
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Storkus
authors.forename: Hideho
authors.initials: H
authors.lastname: Okada