CLINICAL TRIAL: ADENOVIRAL VECTOR DELIVERY OF THE HUMAN INTERLEUKIN-12 CDNA IN M

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在美国，结直肠癌是癌症死亡的第二大原因。目前对转移性结直肠癌患者的标准治疗是联合化疗，尽管有效率高达50%，但很少是完全的，对生存的好处有限。 白介素12是一种由激活的单核细胞和巨噬细胞产生的细胞因子，动物研究表明，它通过增强抗肿瘤免疫反应而具有抗肿瘤活性。广泛的长期目标是在我们的临床研究的基础上进行临床转化研究，该研究表明免疫调节方法与基因治疗相结合在提高荷瘤小鼠的长期存活率和肿瘤侵袭性方面是有效的。具体地说，瘤内注射表达小鼠白细胞介素12的腺病毒载体(Adv.RSV-mIL 12)和针对T细胞刺激受体4-1BB的激动型单抗(Mab-anti-M4-1BB)相结合，能有效地产生抗肿瘤免疫反应，肿瘤消退和长期存活的动物比例为80%-100%。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Colorectal cancer is the second leading cause of cancer deaths in the United States. The current standard treatment for patients with metstatic colorectal cancer is combination chemotherapy, which despite response rates of up to 50%, are rarely complete and produces limited survival benefit. Interleukin-12 is a cytokine produced by activated monocytes and macrophages, and has been shown in animal studies to have antitumoral activity through its ability to enhance antitumor immune responses. The broad, long term objectives are to conduct clinical translational studies based on our peclinical research which showed that combination immunomodulatory approaches with gene therapy were effective in producing long term survival and tumor aggession in tumor-bearing mice. Speficially, the combination of intratumoral delivery of adenoviral vector expressing murine interleukin-12 (Adv.RSV-mIL 12) in combination with an agonistic monoclonal antibody (Mab-anti-m4-1BB) against the T-cell stimulation receptor 4-1BB was effective in producing antitumor immune responses, tumor regression and long term survival in 80-100% of treated animals.