Fundamental Research of immunothejtepy targeting tumor antigen-MUC1 mucin

1.寡肽脉冲的DC上与MUC 1呈递相关的分子来源于MUC 1核心蛋白的寡肽在被APC摄取后被呈递到包括DC在内的一些PBMC群体上。结论：1.与SM 3反应的表位片段可与APC上的HLA I类和II类抗原结合，并可被CTL识别，而不受MHC限制。MUC 1肽体外刺激诱导MUC 1特异性CTL MUC 1特异性CTL可在肺癌患者的PBMC中容易地诱导MUC 1肽。然而，MUC 1特异性CTL的混合淋巴细胞肿瘤细胞培养使用两个同种异体MUC 1阳性癌细胞系在16天内发生凋亡死亡。但DC上的B7-1分子是拯救CTL免于MUC 1介导的凋亡所必需的.靶向MUC 1 mucn的免疫治疗的临床试验4名晚期肺癌患者和3名晚期乳腺癌患者接受了使用MUC 1肽和负载有所述肽的树突状细胞在PBMC中诱导的MUC 1特异性CTL的注射。在2例患者中观察到临床应答（CR 1例患者，PR 1例患者和NC 5例患者）。除轻度发热外，无严重并发症。

1. The molecules on oligopeptides-pulsed DCs associated with MUC1 presentationoligopeptides derived from MUC1 core protein are presented on some populations of PBMCs including DCs following uptake by the APCs. The epitope fragment reactive with SM3 is bound to both HLA class I and class II on the APCs and recognized by CTLs without an MHC-restriction.2. Induction of MUC1-specific CTL by in vitro stimulation with MUC1 peptidesMUC1-specific CTLs can be easily induced in PBMCs from patients with lung cancer, using MUC1 peptides. Whereas, MUC1- specific CTL by mixed-lymphocyte tumor cell culture using two allogeneic MUC1-positive cancer cell lines underwent apoptotic death within 16 days. But B7-1 molecule on DCs is required for rescuing CTL from undergoing apoptotic death mediated by MUC1 mucin.3. Clinical trial of immunotherapy targeting MUC1 mucnFour patient with advanced lung cancer and 3 with advanced breast cancer were received injections of MUC1- specific CTLs induced in PBMCs using MUC1 peptides and dendritic cells loaded with the peptides. Clinical response was observed in 2 patients (CR 1 patient, PR 1 patient and NC 5 patients). Severe complication was not observed in all patients except for slight fever.