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.
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