a Clinical Research Division , Fred Hutchinson Cancer Research Center , Seattle , WA , USA.
b Department of Medicine , University of Washington , Seattle , WA , USA.
Expert Rev Vaccines. 2018 Feb;17(2):107-114. doi: 10.1080/14760584.2018.1419068. Epub 2017 Dec 27.
Synovial Sarcoma (SS) and Myxoid Round Cell Liposarcoma (MRCL) are devastating sarcoma subtypes with few treatment options and poor outcomes in the advanced setting. However, both these diseases may be ideal for novel immunotherapies targeting the cancer-testis antigen, NY-ESO-1.
In this review, we discuss the novel NY-ESO-1 targeted vaccine regimen, CMB305. This regimen uses a unique integration-deficient, dendritic-cell targeting lentiviral vector from the ZVex® platform, LV305, in order to prime NY-ESO-1 specific T cells. LV305 has single agent activity, and, in one case, caused a durable partial response in a refractory SS patient. CMB305 also includes a boost from a NY-ESO-1 protein vaccine given along with a potent toll-like-4 receptor agonist, glycopyranosyl lipid A. CMB305 induces NY-ESO-1 specific T cell responses in both SS and MRC patients and these patients had excellent overall survival (OS) outcomes in the initial phase I study.
CMB305 is a therapeutic vaccine regimen targeting NY-ESO-1 based on the lentiviral vaccine vector, LV305. Phase I studies have proven this vaccine is active immunologically. Data suggesting this vaccine may improve OS for SS and MRCL patients is exciting but early, and on-going work is testing the impact of CMB305 on patient outcomes.
滑膜肉瘤（SS）和黏液样圆形细胞脂肪肉瘤（MRCL）是两种具有破坏性的肉瘤亚型，在晚期阶段治疗选择有限，预后较差。然而，这两种疾病都可能是针对癌症睾丸抗原 NY-ESO-1 的新型免疫疗法的理想选择。
在这篇综述中，我们讨论了新型 NY-ESO-1 靶向疫苗方案 CMB305。该方案使用来自 ZVex®平台的具有独特整合缺陷、靶向树突状细胞的慢病毒载体 LV305，以启动 NY-ESO-1 特异性 T 细胞。LV305 具有单药活性，并且在一种情况下，导致一名难治性 SS 患者出现持久的部分缓解。CMB305 还包括 NY-ESO-1 蛋白疫苗的加强免疫，与一种有效的 Toll 样受体 4 激动剂，糖基脂质 A 联合使用。CMB305 在 SS 和 MRC 患者中诱导 NY-ESO-1 特异性 T 细胞反应，这些患者在初始 I 期研究中具有出色的总生存期（OS）结果。
CMB305 是一种基于慢病毒疫苗载体 LV305 的针对 NY-ESO-1 的治疗性疫苗方案。I 期研究已经证明该疫苗在免疫学上具有活性。提示该疫苗可能改善 SS 和 MRCL 患者 OS 的数据令人兴奋，但仍处于早期阶段，正在进行的工作正在测试 CMB305 对患者结局的影响。
