Determination of the Mechanism of IL-2-Induced Rejection of Intracranial Melanoma Tumors in a Murine Model Using Transduced Tumor Cells
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Authors
Babel, Kelly M.
Issue Date
1996
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
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.
With honors.
Description
viii, 40 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.