Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing 210009, China.
Department of Gynecology & Obstetrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
Int Immunopharmacol. 2017 Nov;52:238-244. doi: 10.1016/j.intimp.2017.09.019. Epub 2017 Sep 23.
Although tumor vaccines have been considered a promising immunotherapy approach, therapeutic tumor vaccines are mostly disappointing in the clinic due to vaccine weak immunogenicity. Cancer stem cells (CSCs) may broaden the antigenic breadth and effectively induce the immune responses against autologous cancer cells. Here we report on the development of the B16F10 CD133CD44CSCs (B16F10 CSCs) vaccine to induce tumor immunity to melanoma in mice. Efficacy of against melanoma was evaluated by analysis of tumor growth and mouse survival. Immunogenicity was assessed by ELISA and flow cytometric assays, including serum cytokines, cytotoxic activity of NK cells and splenocytes in the immunized mice. The results showed that the B16F10 CSC vaccine resulted in tumor shrinkage and mouse lifespan extension. The cytotoxic activity and IFN-γ level were significantly increased in mice immunized with B16F10 CSC vaccine compared with the mice immunized with control vaccines. Additionally, New York esophageal squamous cell carcinoma-1, an efficient tumor associated antigen over-expressed by B16F10 CSCs, was markedly reduced in expression in melanoma tissue, suggesting decrease of CSC subpopulation due to B16F10 CSC vaccination. Collectively, the findings may represent a new powerful approach for treatment of melanoma by B16F10 CSC vaccination.
虽然肿瘤疫苗被认为是一种很有前途的免疫疗法,但由于疫苗的免疫原性较弱,治疗性肿瘤疫苗在临床上大多令人失望。癌症干细胞(CSCs)可能会拓宽抗原的广度,并有效地诱导针对自体癌细胞的免疫反应。在这里,我们报告了开发 B16F10 CD133CD44CSCs(B16F10 CSCs)疫苗以诱导小鼠黑色素瘤肿瘤免疫的情况。通过分析肿瘤生长和小鼠存活来评估针对黑色素瘤的疗效。通过 ELISA 和流式细胞术检测评估免疫原性,包括免疫小鼠的血清细胞因子、NK 细胞和脾细胞的细胞毒性活性。结果表明,B16F10 CSC 疫苗可导致肿瘤缩小和小鼠寿命延长。与用对照疫苗免疫的小鼠相比,用 B16F10 CSC 疫苗免疫的小鼠的细胞毒性活性和 IFN-γ 水平显着增加。此外,B16F10 CSCs 过表达的有效肿瘤相关抗原纽约食管鳞癌细胞-1在黑色素瘤组织中的表达明显降低,这表明由于 B16F10 CSC 接种疫苗,CSC 亚群减少。总之,这些发现可能代表了通过 B16F10 CSC 接种疫苗治疗黑色素瘤的一种新的有力方法。