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一种负载李斯特菌肽的靶向树突状细胞疫苗对转移性黑色素瘤具有卓越的抗肿瘤活性。

Exceptional antineoplastic activity of a dendritic-cell-targeted vaccine loaded with a Listeria peptide proposed against metastatic melanoma.

作者信息

Calderon-Gonzalez Ricardo, Bronchalo-Vicente Lucia, Freire Javier, Frande-Cabanes Elisabet, Alaez-Alvarez Lidia, Gomez-Roman Javier, Yañez-Diaz Sonsóles, Alvarez-Dominguez Carmen

机构信息

Group of Genomics, Proteomics and Vaccines, Marqués de Valdecilla Research Institute (IDIVAL), Santander, Spain.

Dermatology Department, Marqués de Valdecilla University Hospital (HUMV), Santander, Spain.

出版信息

Oncotarget. 2016 Mar 29;7(13):16855-65. doi: 10.18632/oncotarget.7806.

Abstract

Vaccination with dendritic cells (DCs) is proposed to induce lasting responses against melanoma but its survival benefit in patients needs to be demonstrated. We propose a DC-targeted vaccine loaded with a Listeria peptide with exceptional anti-tumour activity to prevent metastasis of melanoma. Mice vaccinated with vaccines based on DCs loaded with listeriolysin O peptide (91-99) (LLO91-99) showed clear reduction of metastatic B16OVA melanoma size and adhesion, prevention of lung metastasis, enhanced survival, and reversion of immune tolerance. Robust innate and specific immune responses explained the efficiency of DC-LLO91-99 vaccines against B16OVA melanoma. The noTable features of this vaccine related to melanoma reduction were: expansion of immune-dominant LLO91-99-specific CD8 T cells that helped to expand melanoma-specific CD8+ T cells; high numbers of tumour-infiltrating lymphocytes with a cytotoxic phenotype; and a decrease in CD4+CD25high regulatory T cells. This vaccine might be a useful alternative treatment for advanced melanoma, alone or in combination with other therapies.

摘要

有人提出用树突状细胞(DC)进行疫苗接种以诱导针对黑色素瘤的持久反应,但其对患者的生存益处尚需证明。我们提出一种装载有具有卓越抗肿瘤活性的李斯特菌肽的DC靶向疫苗,以预防黑色素瘤转移。用基于装载了溶菌酶O肽(91-99)(LLO91-99)的DC的疫苗接种的小鼠,其转移性B16OVA黑色素瘤的大小和黏附明显减少,肺转移得到预防,生存期延长,免疫耐受得以逆转。强大的固有免疫和特异性免疫反应解释了DC-LLO91-99疫苗针对B16OVA黑色素瘤的有效性。这种与黑色素瘤缩小相关的疫苗的显著特征包括:免疫优势的LLO91-99特异性CD8 T细胞的扩增,这有助于扩增黑色素瘤特异性CD8+ T细胞;大量具有细胞毒性表型的肿瘤浸润淋巴细胞;以及CD4+CD25high调节性T细胞的减少。这种疫苗可能是晚期黑色素瘤单独或与其他疗法联合使用的一种有用的替代治疗方法。

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