Enhanced immunity by NeuEDhsp70 DNA vaccine is needed to combat an aggressive spontaneous metastatic breast cancer
Enhanced immunity by NeuEDhsp70 DNA vaccine is needed to combat an aggressive spontaneous metastatic breast cancer
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DOI：
10.1016/j.ymthe.2005.01.003
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发表时间：
2005-06-01
影响因子：
12.4
通讯作者：
You, ZY
中科院分区：
文献类型：
--
作者：
Kim, JH;Majumder, N;You, ZY
肿瘤的快速生长和无情转移需要有效的广泛免疫反应。树突状细胞（dc）在开发肿瘤疫苗中起着至关重要的作用。最近的研究主要集中在修饰肿瘤抗原以靶向树突状细胞，从而在体内有效地诱导免疫反应。在本研究中，将人hsp70融合到大鼠Her2/Neu的细胞外结构域（NeuEDhsp70）以增强侵袭性乳腺肿瘤模型的抗肿瘤免疫。newedhsp70条件下的树突状细胞产生显著的IL-12p40，并在体外有效地向T细胞呈递NeuED抗原。在体内，NeuEDhsp70 DNA疫苗诱导增强的neu特异性抗体和产生ifn - γ的细胞免疫反应。尽管NeuEDhsp70和NeuED DNA疫苗在侵袭性原发性乳腺肿瘤模型中引发了相当的治疗性抗肿瘤免疫，但NeuEDhsp70 DNA疫苗在侵袭性自发性转移性乳腺肿瘤模型中显著提高了生存率并减少了转移。免疫细胞缺失或CD40分子缺失的动物实验结果表明，T细胞和CD40分子在NeuEDhsp70 DNA疫苗诱导的抗肿瘤免疫中起关键作用。这些观察结果表明，NeuEDhsp70 DNA疫苗是一种有前景的试剂，可诱导对侵袭性自发转移性乳腺肿瘤的有效抗肿瘤免疫。
The rapid growth and ruthless metastasis of tumors demand effective broad immune responses. Dendritic cells (DCs) are critical in developing tumor vaccines. Recent investigations have been focused on modifying tumor antigens to target DCs to induce immune responses efficiently in vivo. In this study, human hsp70 was fused to the extracellular domain of rat Her2/Neu (NeuEDhsp70) for enhancing anti-tumor immunity in aggressive breast tumor models. Neu EDhsp 70-conditioned DCs produced significant IL-12p40 and effectively presented NeuED antigens to T cells in vitro. NeuEDhsp70 DNA vaccine induced enhanced Neu-specific antibody and IFN-gamma-producing cellular immune responses in vivo. Although NeuEDhsp70 and NeuED DNA vaccines elicited comparable therapeutic anti-tumor immunity in an aggressive primary breast tumor model, NeuEDhsp70 DNA vaccine significantly increased survival and reduced metastasis in an aggressive spontaneous metastatic breast tumor model. Results from animal experiments with depletion of immune cells or with deficiency of CD40 molecules indicate that T cells and CD40 molecules are critical in the antitumor immunity induced by NeuEDhsp70 DNA vaccine. These observations suggest that NeuEDhsp70 DNA vaccine is a promising reagent to induce potent anti-tumor immunity to an aggressive spontaneous metastatic breast tumor.