Hatano Manabu, Kuwashima Naruo, Tatsumi Tomohide, Dusak Jill E, Nishimura Fumihiko, Reilly Karlyne M, Storkus Walter J, Okada Hideho
Department of Neurological Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.
J Transl Med. 2004 Nov 24;2(1):40. doi: 10.1186/1479-5876-2-40.
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.
一种新型酪氨酸激酶受体EphA2在晚期和转移性癌症中高表达。我们研究了用作为T细胞表位的合成小鼠EphA2(mEphA2)衍生肽进行疫苗接种是否能诱导保护性和治疗性抗肿瘤免疫。方法:C57BL/6小鼠接受皮下(s.c.)接种用被CD8 +(mEphA2671 - 679,mEphA2682 - 689)和CD4 +(mEphA230 - 44)T细胞识别的合成肽脉冲处理的骨髓来源树突状细胞(DC)。从致敏小鼠中收获脾细胞(SPC)以评估针对同基因胶质瘤、肉瘤和黑色素瘤细胞系的细胞毒性T淋巴细胞(CTL)反应的诱导。然后评估这些疫苗预防或治疗肿瘤(皮下注射MCA205肉瘤或B16黑色素瘤;静脉注射B16 - BL6)形成/进展的能力。结果:用mEphA2衍生肽免疫C57BL/6小鼠在SPC中诱导了特异性CTL反应。用mEPhA2肽而非对照卵清蛋白(OVA)肽进行疫苗接种,在皮下和肺转移模型中均预防了EphA2 +或EphA2阴性同基因肿瘤的形成或生长。结论:这些数据表明mEphA2可作为引导抗肿瘤免疫的有吸引力的靶点。mEphA2疫苗影响EphA2阴性肿瘤如B16黑色素瘤的能力可能表明这种有益的免疫可能针对替代的EphA2 +靶细胞,如肿瘤相关血管内皮细胞。