Day-4 myeloid dendritic cells pulsed with whole tumor lysate are highly immunogenic and elicit potent anti-tumor responses.
Day-4 myeloid dendritic cells pulsed with whole tumor lysate are highly immunogenic and elicit potent anti-tumor responses.
复制标题
DOI：
10.1371/journal.pone.0028732
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Coukos G
中科院分区：
文献类型：
--
作者：
Chiang CL;Hagemann AR;Leskowitz R;Mick R;Garrabrant T;Czerniecki BJ;Kandalaft LE;Powell DJ Jr;Coukos G
“第7天”髓样DC通常用于临床。然而，强烈需要更快地开发DC，其具有与“第7天”骨髓DC相同的有效免疫刺激能力，同时使DC制备的时间、劳动力和成本最小化。尽管“2天”DC可以引发肽特异性应答，但它们尚未被证明能够吞噬、加工和呈递复杂的全肿瘤裂解物，而复杂的全肿瘤裂解物可能是比限定的肽更方便和个性化的肿瘤抗原来源。在该临床前研究中，我们评估了第2天、第4天和第7天培养的单核细胞来源的DC的T细胞刺激能力，所述DC负载有通过冻融或通过UVB照射然后冻融制备的SKOV 3细胞全裂解物，并且用脂多糖（LPS）和干扰素（IFN）-γ成熟。评估DC的抗原摄取，并且在用LPS和IFN-γ成熟后，评估DC的CD 80、CD 40、CD 86、ICAM-1和CCR 7的表达，IL-12 p70和IP-10的产生，以及肿瘤特异性T细胞应答的诱导。第4天和第7天的DC表现出相似的吞噬能力，其上级于第2天的DC。成熟的第7天DC表达最高的CD 40和ICAM-1，但成熟的第4天DC产生最多的IL-12 p70和IP-10。重要的是，来自卵巢癌患者的第4天和第7天DC同样强烈地刺激肿瘤特异性T细胞应答。这是第一项证明第4天髓样DC的高免疫原性和强T细胞刺激特性的研究，并为快速开发适用于许多肿瘤类型的有效的全肿瘤裂解物负载的DC疫苗提供了重要的临床前数据。
“Day-7” myeloid DCs are commonly used in the clinic. However, there is a strong need to develop DCs faster that have the same potent immunostimulatory capacity as “Day-7” myeloid DCs and at the same time minimizing time, labor and cost of DC preparations. Although “2 days” DCs can elicit peptide-specific responses, they have not been demonstrated to engulf, process and present complex whole tumor lysates, which could be more convenient and personalized source of tumor antigens than defined peptides. In this preclinical study, we evaluated the T-cell stimulatory capacity of Day-2, Day-4, and Day-7 cultured monocyte-derived DCs loaded with SKOV3 cell whole lysate prepared by freeze-thaw or by UVB-irradiation followed by freeze-thaw, and matured with lipopolysaccharide (LPS) and interferon (IFN)-gamma. DCs were evaluated for antigen uptake, and following maturation with LPS and IFN-gamma, DCs were assessed for expression of CD80, CD40, CD86, ICAM-1 and CCR7, production of IL-12p70 and IP-10, and induction of tumor-specific T-cell responses. Day-4 and Day-7 DCs exhibited similar phagocytic abilities, which were superior to Day-2 DCs. Mature Day-7 DCs expressed the highest CD40 and ICAM-1, but mature Day-4 DCs produced the most IL-12p70 and IP-10. Importantly, Day-4 and Day-7 DCs derived from ovarian cancer patients stimulated equally strongly tumor-specific T-cell responses. This is the first study demonstrating the highly immunogenic and strong T-cell stimulatory properties of Day-4 myeloid DCs, and provided important preclinical data for rapid development of potent whole tumor lysate-loaded DC vaccines that are applicable to many tumor types.
登录
查看更多内容
影响因子：
13
作者：
Neville, Lewis F.;Mathiak, Guenther;Bagasra, Omar
通讯作者：
Bagasra, Omar
影响因子：
3.9
作者：
Gitlitz, BJ;Belldegrun, AS;Figlin, RA
通讯作者：
Figlin, RA
整个肿瘤抗原疫苗。
影响因子：
7.8
作者：
Chiang CL;Benencia F;Coukos G
通讯作者：
Coukos G
影响因子：
82.9
作者：
Nestle, FO;Alijagic, S;Schadendorf, D
通讯作者：
Schadendorf, D
影响因子：
5.8
作者：
Chiang, Cheryl L-L.;Ledermann, Jonathan A.;Chain, Benjamin M.
通讯作者：
Chain, Benjamin M.