Mulé James J
Moffitt Cancer Center, Tampa, FL 33612, USA.
Ann N Y Acad Sci. 2009 Sep;1174:33-40. doi: 10.1111/j.1749-6632.2009.04936.x.
Based on leads from our recent animal studies, we are embarking on a series of new clinical trials to evaluate potential improvements in dendritic cell (DC)-based vaccines for melanoma and pancreatic cancer. The first new strategy involves the use of a powerful chemokine (denoted secondary lymphoid tissue chemokine; SLC/CCL-21), which can both create functioning lymph node-like structures at sites of vaccination with tumor-loaded DCs and dramatically enhance vaccine efficacy in animal tumor models. Using this strategy, we are embarking on a clinical trial in melanoma patients with the intent to create functioning, ectopic, lymph node-like structures to enhance host antitumor immunity. The second strategy, in the setting of pancreatic cancer, involves a gene therapy and immunotherapy combination of a locally administered tumor necrosis factor-alpha gene vector followed by radiation (to induce tumor apoptosis/necrosis) and intratumorally administered monocyte-derived DCs (to uptake and present antigens from dying tumor cells to elicit potent, systemic, antitumor immunity).
基于我们近期动物研究的线索，我们正在开展一系列新的临床试验，以评估基于树突状细胞（DC）的黑色素瘤和胰腺癌疫苗的潜在改进效果。首个新策略涉及使用一种强效趋化因子（称为二级淋巴组织趋化因子；SLC/CCL-21），它既能在用负载肿瘤的DC进行疫苗接种的部位形成功能性淋巴结样结构，又能在动物肿瘤模型中显著提高疫苗效力。采用这一策略，我们正在对黑色素瘤患者开展一项临床试验，旨在创建功能性异位淋巴结样结构，以增强宿主抗肿瘤免疫力。第二个策略是在胰腺癌治疗中，采用局部给药肿瘤坏死因子-α基因载体，随后进行放疗（诱导肿瘤凋亡/坏死）以及瘤内注射单核细胞衍生的DC（摄取并呈递来自垂死肿瘤细胞的抗原，以引发强效的全身抗肿瘤免疫）的基因治疗与免疫治疗相结合的方法。
