Defense Date


Document Type


Degree Name

Doctor of Philosophy


Anatomy & Neurobiology

First Advisor

Randall E. Merchant


Primary brain tumor affects some 18,000 adults in the United States each year (Silverberg et al., 1990; Merchant et al., 1997) and over 30% are high-grade anaplastic astrocytoma or glioblastoma multiforme (GBM) (Parney et al., 1997). According to Kruse et al., 1989, the treatment of patients with recurrent or persistent high-grade gliomas represents a major therapeutic challenge. The use of conventional therapy consisting of surgery, followed by radiation therapy and chemotherapy for gliomas, has been relatively ineffective (Jaecle et al., 1994) despite the fact that these therapies are cytoreductive in nature (Black, 1991). Most malignancies will recur locally but may also reappear at a different site within the brain. A brain tumor, once established, usually continues to outstrip the inhibitory action of any immunobiological defense mechanisms against it. Thus, malignant intracranial (IC) brain tumors represent a lethal neoplastic disease in which treatment has failed to extend the lifespan of afllicted individuals, with a GBM having a median survival rate of less than one year (Harsh et al., 1987).This has prompted a search for other potentially useful methods to better understand the biology of brain tumors as well as better ways to treat them The studies outlined herein, addressed the mechanisms behind the protection against tumor development provided by the various cells of the innate and cellular immune response in a rat brain tumor model. Investigations consisted of: 1) primary (1°) vaccination involving a phenotypic examination and functional analysis of the cells of the innate immune response and the cells of the adaptive immune response infiltrating an RT-2 glioma and the expression of the CD25 receptor; 2) 1° and secondary (2°) vaccination that involved a follow-up on survival as well as the phenotyping of cells of the leukocytic immune response; 3) rechallenge of long-lived rats, from Experiment 2, in the contralateral (left) hemisphere; and 4) acquisition of memory T lymphocytes from vaccinated rats and the use of lymphocyte depletion studies to determine which cells were necessary to provide a protective vaccination against development of tumor. Thus, this study illustrated a potential therapeutic strategy to develop treatments for GBM patients as well as providing protection against development of tumor by the use of vaccines.


Scanned, with permission from the author, from the original print version, which resides in University Archives.


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