Dendritic cell targeting vaccine for HPV-associated cancer
Dendritic cell targeting vaccine for HPV-associated cancer
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DOI：
10.14800/ccm.1482
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发表时间：
2017-01
期刊：
影响因子：
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通讯作者：
Wenjie Yin;D. Duluc;HyeMee Joo;SangKon Oh
中科院分区：
文献类型：
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作者：
Wenjie Yin;D. Duluc;HyeMee Joo;SangKon Oh
树突状细胞（Dendritic cells，DC）是主要的抗原提呈细胞，能够有效地引发和激活细胞免疫应答。因此，将抗原递送到体内DC被认为是一种有前途的策略，可以使我们能够在患者中建立T细胞介导的针对癌症的治疗性免疫。然而，成功开发这种类型的癌症疫苗，可以靶向体内的DC，需要解决一系列悬而未决的问题。这些包括正确选择DC表面受体、特异性DC亚群和DC激活剂，其可以通过促进效应T细胞浸润和保留在肿瘤中以及它们对肿瘤的作用来进一步增强疫苗的功效。用可以抵消肿瘤免疫逃避机制的额外策略补充这些研究领域，也有望增强此类治疗性疫苗对抗癌症的功效。经过十多年的研究，我们得出结论，通过CD 40靶向DC以引起细胞应答的抗原比通过11种其他测试的DC表面受体靶向相同类型的DC的抗原更有效。在最近的工作中，我们进一步证明了用于HPV 16相关癌症的原型疫苗（抗CD 40-HPV16.E6/7，抗人CD 40和HPV16.E6/7蛋白的重组融合蛋白）可以有效地激活来自HPV 16+头颈癌患者血液的HPV16.E6/7特异性T细胞，特别是CD 8 + T细胞。此外，抗CD 40-HPV16.E6/7加poly（I：C）可在人CD 40转基因小鼠中产生针对表达HPV16.E6/7蛋白的TC-1肿瘤的有效治疗性免疫。因此，在这篇手稿中，我们强调了我们最近的研究结果，为HPV 16相关的恶性肿瘤开发新的CD 40靶向免疫疫苗。此外，我们进一步讨论了几个关键的问题，仍然有待解决，以提高我们的原型疫苗对HPV 16相关的恶性肿瘤引起的治疗免疫。
Dendritic cells (DCs) are major antigen presenting cells that can efficiently prime and activate cellular immune responses. Delivering antigens to in vivo DCs has thus been considered as a promising strategy that could allow us to mount T cell-mediated therapeutic immunity against cancers in patients. Successful development of such types of cancer vaccines that can target in vivo DCs, however, requires a series of outstanding questions that need to be addressed. These include the proper selection of which DC surface receptors, specific DC subsets and DC activators that can further enhance the efficacy of vaccines by promoting effector T cell infiltration and retention in tumors and their actions against tumors. Supplementing these areas of research with additional strategies that can counteract tumor immune evasion mechanisms is also expected to enhance the efficacy of such therapeutic vaccines against cancers. After more than a decade of study, we have concluded that antigen targeting to DCs via CD40 to evoke cellular responses is more efficient than targeting antigens to the same types of DCs via eleven other DC surface receptors tested. In recent work, we have further demonstrated that a prototype vaccine (anti-CD40-HPV16.E6/7, a recombinant fusion protein of anti-human CD40 and HPV16.E6/7 protein) for HPV16-associated cancers can efficiently activate HPV16.E6/7-specific T cells, particularly CD8+ T cells, from the blood of HPV16+ head-and-neck cancer patients. Moreover, anti-CD40-HPV16.E6/7 plus poly(I:C) can mount potent therapeutic immunity against TC-1 tumor expressing HPV16.E6/7 protein in human CD40 transgenic mice. In this manuscript, we thus highlight our recent findings for the development of novel CD40 targeting immunotherapeutic vaccines for HPV16-associated malignancies. In addition, we further discuss several of key questions that still remain to be addressed for enhancing therapeutic immunity elicited by our prototype vaccine against HPV16-associated malignancies.