在HLA-A2.1/D(b)-β2m转基因小鼠中对新型乳腺癌相关BA46衍生肽的表征。
Characterization of novel breast carcinoma-associated BA46-derived peptides in HLA-A2.1/D(b)-beta2m transgenic mice.
作者信息
Carmon Lior, Bobilev-Priel Irene, Brenner Baruch, Bobilev Dimitry, Paz Adrian, Bar-Haim Erez, Tirosh Boaz, Klein Tirza, Fridkin Mati, Lemonnier Francois, Tzehoval Esther, Eisenbach Lea
机构信息
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
出版信息
J Clin Invest. 2002 Aug;110(4):453-62. doi: 10.1172/JCI14071.
Abstract
The human milk fat globule membrane protein BA46 (lactadherin) is highly overexpressed in human breast tumors, making it a potential target for tumor immunotherapy. We have identified BA46-derived peptides that contain the motif recognized by the MHC class I molecule HLA-A2.1 and that are processed and presented by human breast carcinoma cells. In mice lacking normal class I molecules but expressing an HLA-A2.1/D(b)-beta2 microglobulin single chain (HHD mice), three peptides elicited specific CTL activity. Two of these peptides also stimulated cytotoxic activity in peripheral blood lymphocytes from HLA-A2.1-positive breast carcinoma patients. Adoptive transfer of HHD-derived bulk CTLs to nude mice bearing human breast carcinoma transplants reduced tumor growth. These peptides therefore represent naturally processed BA46-derived CTL epitopes that can be used in peptide-based antitumor vaccines.
摘要
人乳脂肪球膜蛋白BA46（乳粘连蛋白）在人乳腺肿瘤中高度过表达，使其成为肿瘤免疫治疗的潜在靶点。我们已经鉴定出源自BA46的肽，这些肽含有被MHC I类分子HLA-A2.1识别的基序，并且由人乳腺癌细胞加工和呈递。在缺乏正常I类分子但表达HLA-A2.1/D(b)-β2微球蛋白单链的小鼠（HHD小鼠）中，三种肽引发了特异性CTL活性。其中两种肽还刺激了HLA-A2.1阳性乳腺癌患者外周血淋巴细胞的细胞毒性活性。将源自HHD的大量CTL过继转移到携带人乳腺癌移植瘤的裸鼠中可减少肿瘤生长。因此，这些肽代表了天然加工的源自BA46的CTL表位，可用于基于肽的抗肿瘤疫苗。
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