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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 结直肠癌是美国癌症死亡的第二大原因。 目前转移性结直肠癌患者的标准治疗是联合化疗，尽管反应率高达50%，但很少是完全的，并且产生有限的生存益处。 白细胞介素-12是由活化的单核细胞和巨噬细胞产生的细胞因子，并且已经在动物研究中显示通过其增强抗肿瘤免疫应答的能力而具有抗肿瘤活性。 广泛的，长期的目标是进行临床转化研究的基础上，我们的临床研究表明，联合免疫调节方法与基因治疗是有效的，在产生长期生存和肿瘤侵袭的荷瘤小鼠。 具体而言，肿瘤内递送表达鼠白细胞介素-12（Adv.RSV-mIL 12）的腺病毒载体与针对T细胞刺激受体4-1BB的激动性单克隆抗体（Mab-抗-m4-1BB）的组合在80-100%的治疗动物中有效地产生抗肿瘤免疫应答、肿瘤消退和长期存活。

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.