Allogeneic gastric cancer cell-dendritic cell hybrids induce tumor antigen (carcinoembryonic antigen) specific CD8+T cells
Allogeneic gastric cancer cell-dendritic cell hybrids induce tumor antigen (carcinoembryonic antigen) specific CD8+T cells
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DOI：
10.1007/s00262-005-0684-3
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发表时间：
2006-02-01
影响因子：
5.8
通讯作者：
Ikeguchi, M
中科院分区：
文献类型：
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作者：
Matsumoto, S;Saito, H;Ikeguchi, M
离体生成树突状细胞 (DC) 的方案的开发引发了对其在免疫治疗中潜在用途的深入研究。累积的结果显示了这种治疗对具有高度免疫原性的黑色素瘤的功效。然而，其在其他肿瘤中的疗效仍不清楚。在这项研究中，使用同种异体胃癌细胞-DC杂交体来确定此类免疫疗法对胃癌的疗效。通过聚乙二醇（PEG）和电融合产生DC和同种异体胃癌细胞的融合细胞。这些杂交体用于诱导肿瘤相关抗原 (TAA) 特异性细胞毒性 T 淋巴细胞 (CTL)。 DCs 与同种异体胃癌细胞成功融合，产生杂交细胞。这些杂交细胞具有抗原呈递细胞的功能，因为它们诱导同种异体 CD4+ T 细胞增殖。 MKN-45-DC 杂交细胞刺激的 CD8+ T 细胞在用于免疫时能够杀死 MKN-45。 CTL 杀死了另一种胃癌细胞系 MKN-1 以及黑色素瘤细胞系 888mel，这表明它们识别了共同的肿瘤抗原。 MKN-45特异性CTL可以识别癌胚抗原(CEA)，表明杀伤作用是由于肿瘤抗原以及同种异体抗原。这种方法表明同种异体胃癌细胞-DC杂交体可以在基于DC的免疫疗法中用于胃癌治疗。
The development of protocols for the ex vivo generation of dendritic cells (DCs) has led to intensive research of their potential use in immunotherapy. Accumulating results show the efficacy of this treatment on melanomas which are highly immunogenic. However, its efficacy remains unclear in other tumors. In this study, allogeneic gastric cancer cell-DC hybrids were used to determine the efficacy of this type of immunotherapy in gastric cancer. Fusion cells of DC and allogeneic gastric cancer cells were generated by polyethylene glycol (PEG) and electrofusion. These hybrids were used to induce tumor associated antigen (TAA) specific cytotoxic T lymphocytes (CTLs). The DCs were successfully fused with the allogeneic gastric cancer cells resulting in hybrid cells. These hybrid cells were functional as antigen-presenting cell because they induced allogeneic CD4+ T cells proliferation. CD8+ T cells stimulated by the MKN-45-DC hybrid cells were able to kill MKN-45 when used for immunization. The CTLs killed another gastric cancer cell line, MKN-1, as well as a melanoma cell line, 888mel, suggesting the recognition of a shared tumor antigen. MKN-45 specific CTLs can recognize carcinoembryonic antigen (CEA), indicating that the killing is due to tumor antigens as well as alloantigens. This approach suggests the possible use of allogeneic gastric cancer cell-DC hybrids in DC based immunotherapy for gastric cancer treatment.