The Preuss Foundation Seminar On Vaccine Therapy For Malignant Primary Brain Tumors—February 15–17, 1998, La Jolla, Calif. (1999)

February 25-27, 1998, focused on the issues surrounding the development of a vaccine therapy for MPBT. 2 The invited participants present at the seminar consisted of a prestigious group of basic scientists, neuropathologists, and medical and surgical neuro-oncologists.The meeting Chairmen, Glenn Dranoff (Boston, Mass.) and Darell Bigner (Durham, N.C.), began by defining two overall goals for the seminar.The first goal was to present and evaluate available data in the context of the following questions:1. To what degree will the immunologic privilege of the CNS limit a vaccination therapy? 2.To what extent is the CNS at risk for autoimmune reactions in the context of a vaccination therapy? 3.In what ways are patients with MPBT immunocompromised, and how might this impact on a vaccination therapy?The second goal was to use this information to define the most promising vaccination approaches for MPBT and outline some well-defined clinical trials based on these approaches. Clinical Biology, Etiology, and Genetic Basis of MPBTThe seminar opened with an overview of the clinical biology, etiology, and genetic basis of MPBT.Nicolas de Tribolet (Geneva, Switzerland) and Allan Friedman (Durham, N.C.) reiterated the histopathologic observation that MPBT are diffuse diseases of the brain (Burger et al., 1988;Kelly et al., 1987).Thus, therapies, like surgery or focused radiation therapy, aimed at treating a narrowly restricted volume of brain intrinsically have limited value.In addition, because these therapies are relatively non-specific, patients who obtain responses from these therapies are often devastated by normal brain toxicity (Imperato et al., 1990).Thus, a rationale was provided for seeking a more specific therapeutic approach such as that promised by the intrinsic specificity of the human immune system using active immunotherapy vaccination strategies.Paul Kleihues (Lyon, France) then presented the body of increasing evidence that subtypes of GBM exist and constitute distinct clinicopathologic entities (Biernat et al., 1997a(Biernat et al., , 1997b;;Reyes-Mugica et al., 1997;Tohma et al. 1998;Watanabe et al., 1996).Primary GBM develop in older patients and typically show EGFR overexpression or amplification, PTEN mutations, MDM2 overexpression and P16 deletions.They typically contain large ischemic necrosis and show frequent Fas expression in neoplastic cells surrounding the necrosis.Another entity, secondary GBM, characterized by a progression from lower grade gliomas through to GBM, occur in younger patients, show early P53 mutations, PDGFR overexpression, and, less frequently, loss of DCC expression.Finally, during his presentation, Fred Gage (San Diego, Calif.) reviewed the unique properties of nervous system stem cells and discussed their potential role as brain tumor progenitor cells (Hoshimaru et al., 1996;McKay, 1997).The persistence of proliferative cell populations in the brain suggest a new avenue for research and a new conceptual framework within which to discuss and design past, present, and future experiments in neuro-oncogenesis.Further delineation of these clinical, pathologic, and genetic entities will allow more rational therapy of these dif-