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未成熟的人单核细胞衍生树突状细胞在皮内注射用于黑色素瘤免疫治疗后迅速迁移至引流淋巴结。

Immature human monocyte-derived dendritic cells migrate rapidly to draining lymph nodes after intradermal injection for melanoma immunotherapy.

作者信息

Thomas R, Chambers M, Boytar R, Barker K, Cavanagh L L, MacFadyen S, Smithers M, Jenkins M, Andersen J

机构信息

Center for Immunology and Cancer Research, University of Queensland, Australia.

出版信息

Melanoma Res. 1999 Oct;9(5):474-81. doi: 10.1097/00008390-199910000-00007.

Abstract

Injected antigen-loaded immature monocyte-derived dendritic cells (DCs) may be incapable of migrating from skin to draining lymph nodes for antigen presentation. The in vivo migratory capacity of intradermally administered immature monocyte-derived DCs was therefore investigated during a phase I/II clinical trial for metastatic melanoma. DCs cultured from adherent monocytes in the presence of autologous serum, granulocyte-macrophage colony stimulating factor and interleukin-4 were pulsed with antigen and labelled with technetium-99m hexamethylpropylene-amineoxime (99mTc-HMPAO) ex vivo, then injected intradermally. A 99mTc-HMPAO control containing an equivalent amount of radioactivity was injected into the opposite thigh. The pelvis was then imaged with a gamma camera. The DCs were characterized as immature by functional and phenotypic analysis. Labelled DCs travelled to the draining inguinal lymph nodes within 10 min, and the draining lymph nodes were clearly outlined up to 4 h after injection. Free NmTc outlined draining lymph nodes after 10 min but was cleared from the nodes within 1 h. Thus, immature human monocyte-derived DCs migrate rapidly to and remain in draining lymph nodes after intradermal injection for immunotherapy.

摘要

注射了负载抗原的未成熟单核细胞衍生树突状细胞(DCs)可能无法从皮肤迁移至引流淋巴结进行抗原呈递。因此,在一项针对转移性黑色素瘤的I/II期临床试验中,研究了皮内注射未成熟单核细胞衍生DCs的体内迁移能力。在自体血清、粒细胞-巨噬细胞集落刺激因子和白细胞介素-4存在的情况下,从贴壁单核细胞培养的DCs在体外被抗原脉冲处理并用锝-99m六甲基丙烯胺肟(99mTc-HMPAO)标记,然后进行皮内注射。将含有等量放射性的99mTc-HMPAO对照注射到对侧大腿。然后用γ相机对骨盆进行成像。通过功能和表型分析将DCs表征为未成熟。标记的DCs在10分钟内迁移至引流腹股沟淋巴结,注射后4小时内引流淋巴结轮廓清晰。游离的99mTc在10分钟后勾勒出引流淋巴结,但在1小时内从淋巴结中清除。因此,未成熟的人单核细胞衍生DCs在皮内注射用于免疫治疗后迅速迁移至引流淋巴结并留在其中。

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