Targeting Human Dendritic Cells in a Multiple Myeloma Humanized NOD/SCID Model

负载肿瘤相关抗原（TAA）的过继转移树突状细胞（DC）在动物模型中已被证明可诱导抗肿瘤免疫；然而，它们对癌症患者的治疗效果尚未确定。荷瘤宿主的保护性免疫已经失效，人类DC在肿瘤患者的异常环境中诱导抗肿瘤反应的能力有待进一步研究。由于研究患者DC-肿瘤相互作用的能力有限，包含人类DC和肿瘤的人源化动物模型为获得重要的新信息提供了机会。我们建议在包含人DC的人源化（hu）NOD-SCID模型中将多发性骨髓瘤（MM）发展为人类肿瘤，并利用这种体内MM- humand - scid模型通过纠正人DC-肿瘤相互作用来恢复免疫。这些知识将作为选择和设计一种新的（简化的）基于DC的免疫疗法来治疗癌症患者的快速通道，并将直接转化为我们的MM临床试验项目，有可能基于CD205识别靶向人类DC。

Adoptively transferred dendritic cells (DC) loaded with tumor associated antigen (TAA) have been shown to induce anti-tumor immunity in animal models; however, their therapeutic efficacy in cancer patients has not been established. Protective immunity has failed in the tumor-bearing host and the ability of human DC to induce anti-tumor responses in the abnormal environment of the cancer patient requires further investigation. Due to the limited capacity to investigate the DC-tumor interaction in patients, humanized animal models containing human DC and tumor provide an opportunity to obtain important new information. We propose to develop multiple myeloma (MM) as a human tumor in our humanized (hu)NOD-SCID model containing human DC, and to use this in vivo MM-huNOD-SCID model to restore immunity by correcting the human DC-tumor interaction.This knowledge will act as a fast track to select and design a new (simplified) DC-based immunotherapy to treat cancer patients and will be translated directly into our MM clinical trials program, potentially by targeting human DC based on CD205 recognition.