Determination of the Mechanism of IL-2-Induced Rejection of Intracranial Melanoma Tumors in a Murine Model Using Transduced Tumor Cells
Babel, Kelly M.
MetadataShow full item record
Metastatic brain tumors, which account for greater than one half of all intracranial tumors, are a significant cause of mortality. Current therapies include a combination of surgery, radiation therapy and chemotherapy. Patients with even the best prognostic indicators still die, however, within 18-24 months of diagnosis. In an effort to address this problem, new immunotherapeutic strategies are now being explored to treat brain tumors. In this experiment, the efficacy and mechanism of active IL-2 immunotherapy against a metastatic brain tumor was explored in a murine model. The effects of Interleukin-2 (IL-2), delivered via IL-2 transduced B16-F10 melanoma tumor cells at the site of an intracranial melanoma tumor, were evaluated. Investigations were then carried out to determine which types of immune effector cells were involved in producing the anti-tumor response. C57BL/6 mice with fully functional immune systems (normal mice) were compared to mice depleted of T helper cells (CD4- mice), cytotoxic T cells (CD8-mice) or natural killer cells (NK- mice). Treatment mice were co-injected intracranially with irradiated IL-2 transduced melanoma cells and wild type melanoma cells. Transduced cells were irradiated to prevent replication in vivo, while preserving the ability of the cells to produce IL-2. Survival was assessed. The median survival of normal, NK-, CD8- and CD4- control groups of mice ranged from 14-21 days post intracranial challenge. In comparison, the median survival of normal treatment mice had not yet been reached at 70 days and 66% of the mice were cured of tumor. The median survival of NK- treatment mice and CD8- treatment mice was 25 and 27 days respectively and 50% of the CD4- treatment mice survived greater than 35 days. These results suggest that a profound anti-tumor response is elicited against intracranial B16-F10 melanoma tumors when IL-2 is delivered in a paracrine fashion at the tumor site. They further indicate that initially, IL-2 bypasses the function of CD4 cells, recruiting NK cells and priming CD8 cells to function as the anti-tumor effector cells. After three days, when IL-2 production has ceased, primed CD8 cells become the principal mediators of tumor rejection.With honors.
Showing items related by title, author, creator and subject.
Studies on Tumor Growth Inhibition by Anti-Angiogenic Drugs as Studied on Walker 256 Rat Carcinoma Tumors Grown on the Chorioallantoic Membrane of the Chick Embryo Burkart, Thomas A. (Kalamazoo College, 1989)An assay for the effect of experimental angiostatic drugs (drugs found to inhibit neovascularization) on growing tumors was developed. Walker 256 rat carcinoma cells were grown in culture and implanted on the chorioallantoic ...
Martin, Kelly A. (2002)Cathepsin B (cat B) has been implicated in the degradation of the extracellular matrix. Collagen I is the major component of the bone matrix, which is a component of the extracellular matrix. It has been shown that ...