Fundamental Research of immunothejtepy targeting tumor antigen-MUC1 mucin

1.与MUC1呈递相关的寡肽冲击的DC上的分子来自MUC1核心蛋白的寡肽存在于某些群体的PBMC上，包括被APC摄取的DC。结论1.与SM3结合的表位片段与APC上的HLAI类和II类抗原结合，可被CTL识别，不受MHC限制。用MUC1多肽体外刺激诱导MUC1特异性CTL在肺癌患者的PBMC中使用MUC1多肽可以很容易地诱导出MUC1特异性CTL。然而，用两个MUC1阳性的同种异体癌细胞株混合淋巴细胞培养的MUC1特异性CTL在16天内发生了凋亡性死亡。但树突状细胞上的B7-1分子是拯救CTL免受MUC1粘蛋白介导的细胞凋亡所必需的。4例晚期肺癌患者和3例晚期乳腺癌患者接受MUC1多肽诱导的特异性CTL和负载MUC1多肽的树突状细胞。临床缓解2例(CR1例，PR1例，NC5例)。除轻度发热外，其余患者均未出现严重并发症。

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.