Immunogenetic therapy of human melanoma utilizing autologous tumor cells transduced to secrete granulocyte-macrophage colony-stimulating factor
Immunogenetic therapy of human melanoma utilizing autologous tumor cells transduced to secrete granulocyte-macrophage colony-stimulating factor
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DOI：
10.1089/10430340050015455
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发表时间：
2000-04-10
影响因子：
4.2
通讯作者：
Nickoloff, BJ
中科院分区：
文献类型：
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作者：
Chang, AE;Li, Q;Nickoloff, BJ
我们对5例黑色素瘤患者进行了一项临床研究，以评估逆转录病毒转导的自体肿瘤细胞作为疫苗接种引流淋巴结的免疫生物学效应。患者在不同的四肢接种野生型（WT）和GM-CSF基因转导的肿瘤细胞。约7天后，取出疫苗致敏的淋巴结（VPLN）。与WT疫苗位点相比，在GM-CSF分泌疫苗位点中树突状细胞（DC）的浸润增加。这导致当GM-CSF的血清水平不可检测时，与WT-VPLN相比，从GM-CSF-VPLN收获更多数量的细胞。五名患者中的四名进行了GM-CSF-VPLN细胞的过继转移，所述GM-CSF-VPLN细胞用抗CD 3 MAb和IL-2离体活化和扩增。一名患者具有转移性肿瘤的持久完全缓解。利用细胞因子（IFN-γ、GM-CSF、IL-10）释放测定，GM-CSF-VPLN T细胞在体外暴露于肿瘤抗原时表现出不同的应答。在两名患者中的两名中，GM-CSF-VPLN T细胞应答与匹配的WT-VPLN细胞的T细胞应答不同。该研究记录了作为疫苗给予的GM-CSF转导的肿瘤细胞与WT肿瘤细胞相比的可测量的免疫生物学差异。一名患者中的完全肿瘤缓解为进一步追求这种方法提供了理论基础。
We performed a clinical study of five patients with melanoma to evaluate the immunobiological effects of retrovirally transduced autologous tumor cells given as a vaccine to prime draining lymph nodes, Patients were inoculated with both wild-type (WT) and GM-CSF gene-transduced tumor cells in different extremities. Approximately 7 days later, vaccine-primed lymph nodes (VPLNs) were removed. There was an increased infiltration of dendritic cells (DCs) in the GM-CSF-secreting vaccine sites compared with the WT vaccine sites. This resulted in a greater number of cells harvested from the GM-CSF-VPLNs compared with the WT-VPLNs at a time when serum levels of GM-CSF were not detectable, Four of five patients proceeded to have the adoptive transfer of GM-CSF-VPLN cells secondarily activated and expanded ex vivo with anti-CD3 MAb and IL-2, One patient had a durable complete remission of metastatic tumor. Utilizing cytokine (IFN-gamma, GM-CSF, IL-10) release assays, GM-CSF-VPLN T cells manifested diverse responses when exposed to tumor antigen in vitro. In two of two patients, GM-CSF-VPLN T cell responses were different from those of matched WT-VPLN cells, This study documents measurable immunobiologic differences of GM-CSF-transduced tumor cells given as a vaccine compared with WT tumor cells, The complete tumor remission in one patient provides a rationale to pursue this approach further.