Potent CTL induction by a whole cell pertussis vaccine in anti-tumor peptide immunotherapy
Potent CTL induction by a whole cell pertussis vaccine in anti-tumor peptide immunotherapy
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DOI：
10.1111/j.1348-0421.2007.tb03957.x
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发表时间：
2007-01-01
影响因子：
2.6
通讯作者：
Udaka, Keiko
中科院分区：
文献类型：
--
作者：
Yano, Arisa;Komatsu, Toshihiro;Udaka, Keiko
据报道，针对肿瘤的基于肽的免疫疗法有希望但有限的临床反应。为了诱导更有效的溶细胞 CD8 T 细胞反应，我们研究了使用百日咳博德特氏菌疫苗作为肽免疫佐剂。已知全细胞 (Wc) 疫苗会诱导 Th1 型免疫反应，而无细胞 (Ac) 疫苗则倾向于诱导 Th2 型免疫反应。百日咳博德特氏菌的自然感染有助于宿主群体维持强大的 Th1 记忆。为了检查百日咳疫苗的佐剂活性，我们用卵清蛋白肽作为模型肿瘤抗原对小鼠进行免疫，并监测抗肿瘤活性的发展。添加 Ac 或 Wc 疫苗有助于扩增特定的 CD8 T 细胞。然而，诱导的细胞溶解活性存在显着差异，其中 Wc 疫苗优于 Ac。 Wc 疫苗在诱导体内肿瘤排斥方面也更有效。佐剂活性不仅对卵清蛋白有效，而且当靶向内源性肿瘤抗原（Wilms 肿瘤 1 基因产物）时也很明显。这些结果表明，虽然Wc疫苗与肿瘤细胞不具有相同的抗原特异性，但它可以作为肽免疫位点的佐剂帮助开发高溶细胞性CD8 T细胞。
Promising yet limited clinical responses have been reported for peptide based immunotherapy against tumors. In order to induce more potent cytolytic CD8 T cell responses, we investigated the use of Bordetella pertussis vaccine as an adjuvant for peptide immunization. A whole cell (Wc) vaccine has been known to induce a Th1 biased immune response while an acellular (Ac) vaccine tends to induce that of the Th2 type. Natural infection by B. pertussis helps to maintain a robust Th1 memory in the host population. To examine the adjuvant activity of the pertussis vaccine, we immunized mice with an ovalbumin peptide as a model tumor antigen, and monitored the development of anti-tumor activities. The addition of either the Ac or the Wc vaccine helped expand the specific CD8 T cells. However, there was a marked difference in the induced cytolytic activity where the Wc vaccine was superior to the Ac. The Wc vaccine was also more effective in inducing in vivo tumor rejection. The adjuvant activity was not only effective against ovalbumin, but was also evident when an endogenous tumor antigen, Wilms' tumor 1 gene product, was targeted. These results indicate that, although the Wc vaccine does not share the same antigen specificity with tumor cells, it can aid in the development of highly cytolytic CD8 T cells as an adjuvant at the site of peptide immunization.