Gilley Ryan P, Dube Peter H
Department of Microbiology, Immunology and Molecular Genetics, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, United States.
Oncotarget. 2020 Feb 18;11(7):740-754. doi: 10.18632/oncotarget.27490.
Melanoma continues to be a significant health concern worldwide despite recent improvements in treatment. Unlike many other prominent cancers, melanoma incidence in both men and women increased over the past decade in the U. S. and much of the developed world. The single greatest risk factor for melanoma is damage from ultraviolet radiation associated with lifestyle. The lifestyle component suggests that although melanoma risk can be minimized with behavioral changes, vaccinating high-risk individuals against melanoma may be the most efficacious preventative method. Accordingly, using a highly attenuated, double-mutant strain expressing a tumor-associated antigen, we obtained significant protection against melanoma in a mouse model. The -based vaccine induced protection through antigen-specific CD8+ T-cells inducing both a protective primary and a memory T-cell response. Vaccinated animals were significantly protected from melanoma. When used in conjunction with checkpoint blockade treatment, the vaccine substantially reduced tumor size and number relative to animals receiving checkpoint blockade (CPB) alone. This study provides evidence that CPB treatment synergizes with a -based melanoma vaccine to enhance vaccine-mediated protection.
尽管近期治疗有所改善，但黑色素瘤仍是全球范围内一个重大的健康问题。与许多其他主要癌症不同，在美国和许多发达国家，过去十年中男性和女性的黑色素瘤发病率均有所上升。黑色素瘤最大的单一风险因素是与生活方式相关的紫外线辐射造成的损害。生活方式这一因素表明，虽然通过行为改变可将黑色素瘤风险降至最低，但为高危个体接种黑色素瘤疫苗可能是最有效的预防方法。因此，我们使用一种表达肿瘤相关抗原的高度减毒双突变株，在小鼠模型中获得了对黑色素瘤的显著保护作用。该疫苗通过抗原特异性CD8 + T细胞诱导保护性的初始和记忆T细胞反应，从而产生保护作用。接种疫苗的动物对黑色素瘤有显著的抵抗力。与单独接受检查点阻断（CPB）治疗的动物相比，当与检查点阻断治疗联合使用时，该疫苗可显著减小肿瘤大小并减少肿瘤数量。这项研究提供了证据，表明CPB治疗与基于[未提及疫苗名称]的黑色素瘤疫苗协同作用，可增强疫苗介导的保护作用。
