The shared tumor-associated antigen cytochrome P4501B1 is recognized by specific cytotoxic T cells
The shared tumor-associated antigen cytochrome P4501B1 is recognized by specific cytotoxic T cells
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DOI：
10.1182/blood-2003-05-1374
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发表时间：
2003-11-01
期刊：
影响因子：
20.3
通讯作者：
Schultze, JL
中科院分区：
文献类型：
--
作者：
Maecker, B;Sherr, DH;Schultze, JL
细胞色素P450 1B1 （CYP1B1）是一种药物代谢的肝外酶，最近被证明在多种类型的癌症中过度表达。这些肿瘤相关基因可能是抗癌治疗，特别是癌症免疫治疗的有用靶点。我们在HLA-A2转基因小鼠中鉴定了HLA-A*0201结合肽和一个自然加工和呈递的T细胞表位，能够诱导cyp1b1特异性细胞毒性T淋巴细胞（ctl）。此外，在健康供体和癌症患者中证实了cyp1b1特异性T细胞的诱导作用。这些T细胞有效地裂解了同源肽脉冲的靶细胞。更重要的是，hla - a2匹配的肿瘤细胞系和原发恶性细胞也能被cyp1b1特异性ctl识别。这些发现构成了达纳法伯癌症研究所进行的一项1期临床试验的基础，该试验探索了一种基于dna的编码CYP1B1的载体，用于广泛适用的癌症免疫治疗。(C) 2003年由美国血液病学会出版。
Cytochrome P450 1B1 (CYP1B1), a drug-metabolizing extrahepatic enzyme, was recently shown to be overexpressed in multiple types of cancer. Such tumor-associated genes may be useful targets for anticancer therapy, particularly cancer immunotherapeutics. We identified HLA-A*0201-binding peptides and a naturally processed and presented T-cell epitope capable of inducing CYP1B1-specific cytotoxic T lymphocytes (CTLs) in HLA-A2 transgenic mice. Furthermore, the induction of CYP1B1-specific T cells was demonstrated in healthy donors and cancer patients. These T cells efficiently lysed target cells pulsed with the cognate peptide. More important, HLA-A2-matched tumor cell lines and primary malignant cells were also recognized by CYP1B1-specific CTLs. These findings form the basis of a phase 1 clinical trial exploring a DNA-based vector encoding CYP1B1 for widely applicable cancer immunotherapy conducted at the Dana-Farber Cancer Institute. (C) 2003 by The American Society of Hematology.