Superior anti-tumor protection and therapeutic efficacy of vaccination with allogeneic and semiallogeneic dendritic cell/tumor cell fusion hybrids for murine colon adenocarcinoma
Superior anti-tumor protection and therapeutic efficacy of vaccination with allogeneic and semiallogeneic dendritic cell/tumor cell fusion hybrids for murine colon adenocarcinoma
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DOI：
10.1007/s00262-006-0252-5
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发表时间：
2007-07-01
影响因子：
5.8
通讯作者：
Kuroda, Yoshikazu
中科院分区：
文献类型：
--
作者：
Yasuda, Takashi;Kamigaki, Takashi;Kuroda, Yoshikazu
通过树突状细胞（DC）/肿瘤细胞融合杂交体（DC/TC杂交体）的癌症免疫治疗已显示通过诱导针对多种肿瘤相关抗原的免疫应答而引起有效的抗肿瘤作用。在本研究中，我们比较了用CT 26 CL 25结肠癌细胞接种BalB/c小鼠（H-2（d））的抗肿瘤效果，所述CT 26 CL 25结肠癌细胞已经与来自BalB/c小鼠的同基因DC、来自C57 BL/6小鼠的同种异体DC（H-2（B））或来自B6 D2 F1小鼠的半同种异体DC（H-2（B/d））融合。半同种异体或同种异体DC/TC混合物预免疫诱导完全保护免受肿瘤攻击，而同基因DC/TC混合物预免疫的小鼠仅部分保护（75%肿瘤排斥）。相对于同基因DC/TC杂交体（67.8 +/- 6.3），用半同种异体或同种异体DC/TC杂交体免疫后，静脉内肿瘤注射后的肺转移的平均数量显著降低（8.3 +/- 7.9或16.3 +/- 3.5，平均值+/- SD）。这些数据表明，用半同种异体DC/TC杂交体接种导致最大的抗肿瘤功效。体内研究显示的抗肿瘤作用实际上是通过使用五聚体测定评估的对gp 70和β-半乳糖苷酶两者特异性的诱导CTL的频率来实现的。在测试的融合疫苗中，半同种异体DC/TC杂交体诱导的Th 1细胞因子IFN-γ与Th 2细胞因子IL-10的比率最高。此外，同种异体或半同种异体DC/TC杂交引起了显着更强的NK活性比同基因DC/TC杂交。这些发现表明，在临床环境中，源自健康供体的DC（其通常表征为比同种异体更半同种异体）可能比自体DC更能够在用DC/TC杂合体接种中诱导有希望的抗肿瘤作用。
Cancer immunotherapy by dendritic cell (DC)/tumor cell fusion hybrids (DC/TC hybrids) has been shown to elicit potent anti-tumor effects via the induction of immune responses against multiple tumor-associated antigens. In the present study, we compared the anti-tumor effects of vaccinating Balb/c mice (H-2(d)) with CT26CL25 colon carcinoma cells that had been fused with either syngeneic DCs from Balb/c mice, allogeneic DCs from C57BL/6 mice (H-2(b)) or semiallogeneic DCs from B6D2F1 mice (H-2(b/d)). Preimmunization with either semiallogeneic or allogeneic DC/TC hybrids induced complete protection from tumor challenge, whereas mice preimmunized with syngeneic DC/TC hybrids were only partially protected (75% tumor rejection). The average number of pulmonary metastases after intravenous tumor injection decreased significantly following immunization with semiallogeneic or allogeneic DC/TC hybrids (8.3 +/- 7.9 or 16.3 +/- 3.5, mean +/- SD) relative to syngeneic DC/TC hybrids (67.8 +/- 6.3). These data demonstrate that vaccination with semiallogeneic DC/TC hybrids resulted in the greatest anti-tumor efficacy. Anti-tumor effects showed by in vivo studies were virtually accomplished by the frequency of induced CTLs specific to both gp70 and beta-galactosidase assessed by using pentameric assay. Among the fusion vaccines tested, semiallogeneic DC/TC hybrids induced the highest ratio of Th1 cytokine IFN-gamma to Th2 cytokine IL-10. In addition, allogeneic or semiallogeneic DC/TC hybrids elicited a significantly stronger NK activity than syngeneic DC/TC hybrids. These findings suggest that in clinical settings, DCs derived from a healthy donor (which are generally characterized as more semiallogeneic than allogeneic) may be more capable than autologous DCs of inducing promising anti-tumor effects in vaccinations with DC/TC hybrids.