Targeting of 111In-Labeled Dendritic Cell Human Vaccines Improved by Reducing Number of Cells
Targeting of 111In-Labeled Dendritic Cell Human Vaccines Improved by Reducing Number of Cells
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DOI：
10.1158/1078-0432.ccr-12-1879
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发表时间：
2013-03-15
影响因子：
11.5
通讯作者：
de Vries, I. Jolanda M.
中科院分区：
文献类型：
--
作者：
Aarntzen, Erik H. J. G.;Srinivas, Mangala;de Vries, I. Jolanda M.
目的：抗癌树突状细胞（DC）疫苗需要树突状细胞转移到淋巴结（LN）以触发免疫反应。然而，这些迁移率通常非常低。提高体外生成的dc对LNs的靶向性可能会提高疫苗效力并降低成本。我们研究了不同条件下DC在人体内的迁移。实验设计：以HLA-A*02:01黑色素瘤患者为研究对象，接种含有酪氨酸酶、gp100多肽和锁孔帽贝血青素（NCT00243594）的成熟dc。在这项研究中，患者接受了111个in标记的成熟dc的额外皮内疫苗接种。注射部位用未装载、活化的dc、TNF α或咪喹莫特进行预处理；同时注射粒细胞巨噬细胞集落刺激因子或少量注射dc。用闪烁成像法测量迁移，并与患者内对照疫苗接种进行比较。在离体组织模型中，我们使用F-19 MRI在长达12小时的时间内测量了ccl21引导的F-19标记dc的迁移，以补充我们的患者数据。结果：注射部位的预处理诱导了局部炎症反应，但没有提高迁移率。在体外和体内，每次注射细胞数减少到5 × 10(6)个或更少的细胞可以改善迁移。此外，闪烁成像技术还不足以研究如此少量的in -111标记的dc在体内的迁移。结论：细胞密度的降低，而不是注射部位的预处理，是促进体内dc向LNs迁移的关键。临床癌症研究；19 (6);1525 - 33所示。(c) 2013年aacr。
Purpose: Anticancer dendritic cell (DC) vaccines require the DCs to relocate to lymph nodes (LN) to trigger immune responses. However, these migration rates are typically very poor. Improving the targeting of ex vivo generated DCs to LNs might increase vaccine efficacy and reduce costs. We investigated DC migration in vivo in humans under different conditions.Experimental Design: HLA-A*02:01 patients with melanoma were vaccinated with mature DCs loaded with tyrosinase and gp100 peptides together with keyhole limpet hemocyanin (NCT00243594). For this study, patients received an additional intradermal vaccination with 111 In-labeled mature DCs. The injection site was pretreated with nonloaded, activated DCs, TNF alpha, or Imiquimod; granulocyte macrophage colony-stimulating factor was coinjected or smaller numbers of DCs were injected. Migration was measured by scintigraphy and compared with an intrapatient control vaccination. In an ex vivo tissue model, we measured CCL21-directed migration of F-19-labeled DCs over a period of up to 12 hours using F-19 MRI to supplement our patient data.Results: Pretreatment of the injection site induced local inflammatory reactions but did not improve migration rates. Both in vitro and in vivo, reduction of cell numbers to 5 x 10(6) or less cells per injection improved migration. Furthermore, scintigraphy is insufficient to study migration of such small numbers of In-111-labeled DCs in vivo.Conclusion: Reduction of cell density, not pretreatment of the injection site, is crucial for improved migration of DCs to LNs in vivo. Clin Cancer Res; 19(6); 1525-33. (C) 2013 AACR.