: Colorectal cancer is the second leading cause of cancer death in the US. There is a 40 percent recurrence in patients treated surgically. Patients with distal metastatic disease have a low 5 yr survival rate with current chemotherapy. Therefore there is a critical need for improved options in the adjuvant setting. The principal goal of this SBIR Phase I proposal is to identify a panel of attenuated Listeria monocytogenes (Listeria) strains that can potentiate the immune response to cellular vaccines for colon cancer. Preliminary studies have suggested that Listeria administered following a therapeutic vaccination can target anti-tumor immune response specifically to liver metastases in a murine model of metastatic colon cancer, increasing the effectiveness of the vaccine by almost 5-fold. The various Listeria strains will be screened for relative pathogenicity and immunogenicity that characterize the innate and adaptive immune response. The immune response to these strains will also be assessed in the murine colorectal liver metastasis model. Appropriate attenuated strains of Listeria will be constructed to secrete GM-CSF and be evaluated for their ability to further augment the immune response to the vaccine in mice. Ultimately, this work will lead to novel adjuvant approaches to treating patients with advanced colon cancer.
| Le, Dung T; Brockstedt, Dirk G; Nir-Paz, Ran et al. (2012) A live-attenuated Listeria vaccine (ANZ-100) and a live-attenuated Listeria vaccine expressing mesothelin (CRS-207) for advanced cancers: phase I studies of safety and immune induction. Clin Cancer Res 18:858-68 |
