Jäger Elke, Karbach Julia, Gnjatic Sacha, Neumann Antje, Bender Armin, Valmori Danila, Ayyoub Maha, Ritter Erika, Ritter Gerd, Jäger Dirk, Panicali Dennis, Hoffman Eric, Pan Linda, Oettgen Herbert, Old Lloyd J, Knuth Alexander
Ludwig Institute Clinical Trial Center, Medizinische Klinik II, Hämatologie-Onkologie, Krankenhaus Nordwest, Steinbacher Hohl 2-26, 60488 Frankfurt, Germany.
Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14453-8. doi: 10.1073/pnas.0606512103. Epub 2006 Sep 19.
NY-ESO-1 is a cancer/testis antigen expressed in a range of human malignancies, and a number of vaccine strategies targeting NY-ESO-1 are being developed. In the present study, the safety and immunogenicity of recombinant vaccinia-NY-ESO-1 and recombinant fowlpox-NY-ESO-1 were analyzed in a series of 36 patients with a range of different tumor types. Each construct was first tested individually at two different dose levels and then in a prime-boost setting with recombinant vaccinia-NY-ESO-1 followed by recombinant fowlpox-NY-ESO-1. The vaccines were well tolerated either individually or together. NY-ESO-1-specific antibody responses and/or specific CD8 and CD4 T cell responses directed against a broad range of NY-ESO-1 epitopes were induced by a course of at least four vaccinations at monthly intervals in a high proportion of patients. CD8 T cell clones derived from five vaccinated patients were shown to lyse NY-ESO-1-expressing melanoma target cells. In several patients with melanoma, there was a strong impression that the natural course of the disease was favorably influenced by vaccination.
NY-ESO-1是一种在多种人类恶性肿瘤中表达的癌胚抗原,目前正在开发多种针对NY-ESO-1的疫苗策略。在本研究中,对36例患有不同肿瘤类型的患者进行了重组痘苗病毒-NY-ESO-1和重组禽痘病毒-NY-ESO-1的安全性和免疫原性分析。每种构建体首先在两个不同剂量水平上单独进行测试,然后在初免-加强设置中,先用重组痘苗病毒-NY-ESO-1进行初免,随后用重组禽痘病毒-NY-ESO-1进行加强免疫。这些疫苗单独或联合使用时耐受性良好。在高比例的患者中,通过至少每月一次的四次接种疗程,诱导出针对广泛NY-ESO-1表位的NY-ESO-1特异性抗体反应和/或特异性CD8和CD4 T细胞反应。来自五名接种疫苗患者的CD8 T细胞克隆显示能够裂解表达NY-ESO-1的黑色素瘤靶细胞。在一些黑色素瘤患者中,强烈感觉到接种疫苗对疾病的自然进程产生了有利影响。