The purpose of this application is to support the development of Dr. Mark Jennings as an academic pediatric neurooncologist, with a clinical emphasis on the management of pediatric brain tumors, and a research emphasis on the immunobiology of pediatric brain tumors. The immunologic investigation proposed is a continuation of serologic analysis conducted by the candidate since July 1983. Murine monoclonal antibodies (MAB) are being generated against human Medulloblastomas, Neuroblastomas and Anaplastic Astrocytomas.
The specific aims are the identification of tumor-restricted and neuroglial differentiation antigens and the development of monoclonal antibody imaging and immunotherapy. Selected antibodies are to be developed for three areas of application. First is the construction of a schema of differentiation among primitive neuroectodermal tumors which would reflect neuroglial maturation steps. Second is the neuropathologic investigation of the cell surface antigens of primary central nervous system (CNS) tumors in order to develop a prognostically relevant classification. Thirdly, antibodies with sufficient specificity are to be evaluated for eventual development in clinical diagnostic imaging and therapy. The accomplishment of this requires: (1) the establishment of new medulloblastoma cell lines, collection and maintenance of existent neuroblastoma and astrocytoma lines, (2) hybridoma technology, (3) serologic, (4) immunohistochemical techniques to define the specificity of the antibodies produced, (5) biochemical methods to evaluate the nature of the antigens identified by the antibodies and (6) genetic analysis beginning with the chromosomal assignment through somatic cell genetic analysis. (7) Eventually MAB imaging and immunotherapy will be developed. In the case of therapy both cytotoxic antibodies and noncytotoxic antibodies conjugated with a toxin or radioisotope will be studied. This broad yet directed training is critical preparation for a career in academic medicine emphasizing clinical investigation in tumor immunology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08NS000986-02
Application #
3083596
Study Section
Neurological Disorders Program Project Review A Committee (NSPA)
Project Start
1985-07-01
Project End
1990-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Memorial Hospital for Cancer & Allied Di
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10021
Jennings, M T; Kaariainen, I T; Gold, L et al. (1994) TGF beta 1 and TGF beta 2 are potential growth regulators for medulloblastomas, primitive neuroectodermal tumors, and ependymomas: evidence in support of an autocrine hypothesis. Hum Pathol 25:464-75
Jennings, M T; Slatkin, N; D'Angelo, M et al. (1993) Neoplastic meningitis as the presentation of occult primitive neuroectodermal tumors. J Child Neurol 8:306-12
Johnson, M D; Jennings, M T; Gold, L I et al. (1993) Transforming growth factor-beta in neural embryogenesis and neoplasia. Hum Pathol 24:457-62
Jennings, M T; Jennings, D L; Ebrahim, S A et al. (1992) In vitro karyotypic and immunophenotypic characterisation of primitive neuroectodermal tumours: similarities to malignant gliomas. Eur J Cancer 28A:762-6
Jennings, M T; Maciunas, R J; Carver, R et al. (1991) TGF beta 1 and TGF beta 2 are potential growth regulators for low-grade and malignant gliomas in vitro: evidence in support of an autocrine hypothesis. Int J Cancer 49:129-39
Jennings, M T; Asadourian, L L; Jennings, V D et al. (1990) Factor analysis of the immunophenotypes of astrocytomas and malignant gliomas: correlations with tumor grade and patient survival. J Neurooncol 9:265-73
Jennings, M T; Jennings, V D; Asadourian, L L et al. (1989) Five novel cell surface antigens of CNS neoplasms. J Neurol Sci 89:63-78
Jennings, M T; Jennings, V D; Asadourian, L L et al. (1989) Antigenic phenotypes of cultured malignant astrocytomas: identification of lineage-consistent, lineage-independent and putative tumor-restricted antigenic expression. J Neurol Sci 89:79-92