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

Journal of Translational Medicine

Hideho Okada⁴  Walter J Storkus¹  Karlyne M Reilly²  Fumihiko Nishimura⁴  Jill E Dusak⁴  Tomohide Tatsumi¹  Naruo Kuwashima³  Manabu Hatano⁴ 

[1] Department of Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA, 15213, USA;Genetic Modifiers of Tumorigenesis Section, Mouse Cancer Genetics Program, National Cancer Institute at Frederick, West 7th Street at Fort Detrick, PO Box B, Building 560, Room 32-31B, Frederick, MD 21702-1201, USA;Department of Neurological Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA, 15213, USA;Brain Tumor Program, University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Pittsburgh, PA, 15213, USA

关键词: melanoma;    cancer vaccines;    dendritic cells;    EphA2;   

Others  :  1208522
DOI  :  10.1186/1479-5876-2-40

 received in 2004-10-11, accepted in 2004-11-24,  发布年份 2004

【 摘 要 】

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+ (mEphA2_671–679, mEphA2_682–689) and CD4+ (mEphA2_30–44) 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.

【 授权许可】

   
2004 Hatano et al; licensee BioMed Central Ltd.

【 图 表 】

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