Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>Pancreatic cancer is difficult to treat due to its late diagnoses and limited treatment options. Strategies capable of reducing tumor mass so that patients are eligible for tumor resection, i.e. the Whipple procedure, and strategies for reducing metastatic deposits with immunotherapy are needed. New immunotherapy techniques can provide an alternative to modern chemotherapy, radiation, or surgical options which have not been able to reduce pancreatic cancer mortality. IL-12 has been discovered to be a potent agent in the development of anti-tumor immunity through its ability to stimulate the activities of cytotoxic T lymphocytes, NK cells, and macrophages while promoting Th1 differentiation. We have previously discovered that a bioadhesive chitosan/IL-12 combination can aggressively eliminate implanted tumors in murine models. Chitosan is a non-toxic and degradable polysaccharide derived from crustacean shells that shows great potential for use in immunotherapy models due to its unique binding properties. Here, ability of chitosan/IL-12 vaccinations to slow the growth of a pancreatic adenocarcinoma cells in vivo was investigated. C57BL/6 mice received subcutaneous inoculations with Panc02 cells. After Panc02 tumors became visible, the mice received 4 weekly intratumoral immunotherapy treatments with either saline or chitosan/IL-12. There was a prominent delay in the tumor growth of the chitosan/IL-12 group at all stages of the treatment. Seven days after the second treatment, control mice had an average tumor volume of 180mm3 and treatment mice tumors became undetectable. Seven days after the fourth treatment, the control mice had an average tumor volume of 743mm3 and treatment mice had an average tumor volume of 221mm3. Cell proliferation assays showed that IL-12 had no direct effect on the Panc02 cell line. However, interferon-γ, a cytokine whose production is induced by IL-12, reduced the growth of Panc02 cells in vitro. These data shows that chitosan/IL-12 may be an effective immunotherapy for pancreatic cancer and also that IL-12 is not directly cytotoxic, but rather, it initiates an effector response capable of inhibiting pancreatic tumors.</jats:p>
<jats:p>Citation Format: Haley K. Perlow, Lirong Yang, David Zaharoff. Pancreatic cancer immunotherapy with chitosan/IL-12. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2581. doi:10.1158/1538-7445.AM2014-2581</jats:p>