Immunity to breast cancer in mice immunized with fibroblasts transfected with a cDNA expression library derived from small numbers of breast cancer cells.

Immunity to breast cancer in mice immunized with fibroblasts transfected with a cDNA expression library derived from small numbers of breast cancer cells.
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用源自少量乳腺癌细胞的 cDNA 表达文库转染的成纤维细胞进行免疫接种的小鼠对乳腺癌的免疫力。

DOI:
10.1038/sj.cgt.7700853
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发表时间:
2005
期刊:
Cancer gene therapy.
影响因子:
--
通讯作者:
Cohen,EdwardP
Cohen,EdwardP
中科院分区:
--
文献类型:
--
作者:
SungKim,Tae;Cohen,EdwardP

文献摘要

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乳腺癌的早期免疫治疗增加了成功的可能性。在这里,在小鼠模型中,我们报告了一种新的策略,使疫苗能够从微克量的肿瘤组织中制备。通过将来自相对少量的乳腺癌细胞的cDNA表达文库转移到高度免疫原性的细胞系中来制备疫苗,在所述细胞系中表达指定TAA的基因。由于转移的DNA在受体细胞分裂时被整合和复制,因此疫苗细胞的数量可以方便地扩增用于重复免疫。将从C3 H/He小鼠(H-2k)中自发产生的乳腺癌制备的cDNA表达文库转移到源自C3 H/He小鼠的小鼠成纤维细胞系中。为了增强其非特异性免疫原性,在DNA转移之前对成纤维细胞进行遗传修饰以分泌IL-2并表达同种异体MHC I类H-2K b-决定簇。C3 H/He小鼠,对乳腺癌细胞的生长高度敏感,用cDNA转染的细胞免疫。在小鼠中产生了强大的乳腺癌特异性CD 8 + T细胞介导的免疫力,提高了类似治疗策略可用于在疾病早期治疗乳腺癌患者的可能性。
Immunotherapy of breast cancer at an early stage of the disease increases the likelihood of success. Here, in a mouse model, we report a new strategy that enables vaccines to be prepared from microgram amounts of tumor tissue. The vaccine is prepared by transfer of a cDNA expression library from relatively small numbers of breast cancer cells into a highly immunogenic cell line, where genes specifying TAA are expressed. As the transferred DNA is integrated and replicated as the recipient cells divide, the number of vaccine cells can be conveniently expanded for repeated immunizations. A cDNA expression library prepared from a breast cancer that arose spontaneously in a C3H/He mouse (H-2 k) was transferred into a mouse fibroblast cell line derived from C3H/He mice. To augment their nonspecific immunogenic properties, the fibroblasts were genetically modified before DNA transfer to secrete IL-2 and to express allogeneic MHC class I H-2K b-determinants. C3H/He mice, highly susceptible to growth of the breast cancer cells, were immunized with the cDNA-transfected cells. Robust breast cancer-specific CD8+ T-cell-mediated immunity was generated in the mice, raising the possibility that an analogous treatment strategy could be used to treat breast cancer patients at an early stage of the disease.