This proposal outlines two closely related projects, (1) production and evaluation of monoclonal antibodies that interfere with or mimic in vitro regulation of survival, growth and differentiation of cultured human neuroblastoma, (2) development of techniques to identify and eliminate neuroblastoma from bone marrow for antologous transplantation. The effects of humoral factors on the regulation of growth and differentiation of cultured human neuroblastoma (CHNB) cells will be examined by assay of clonal growth, morphological differentiation and phosphorylation of specific cell proteins. A panel of mouse monoclonal antibodies that bind to cell surface antigens of several CHNB cell lines will be generated. Effects on protein phosphorylation will be assayed to select mouse monoclonal antibodies that mimic or interfere with the biological actions of regulatory factors. In addition, mouse monoclonal antibodies that identify CHNB cell surface differentiation antigens will be generated. These monoclonal antibodies will be used to investigate growth and differentiation of neuroblastoma. Also, the therapeutic potential of these antibodies will be investigated. The antibodies will also be used to develop methods to identify and eliminate metastatic neuroblastoma cells in bone marrow in vitro, prior to treatment of neuroblastoma with autologous bone marrow transplantation. Monoclonal antibodies will be used to selectively kill neuroblastoma by antibody dependent, complement mediated cytotoxicity. Assays to detect and quantify neuroblastoma in bone marrow will use (1) monoclonal antibodies, binding of which will be detected by a sensitive two color immunofluorescence flow cytometric technique, and (2) selective growth of tumor cell colonies in soft agar.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS022039-03
Application #
3403925
Study Section
Pathology A Study Section (PTHA)
Project Start
1985-04-01
Project End
1988-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Rochester
Department
Type
School of Medicine & Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
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Arguello, F; Furlanetto, R W; Baggs, R B et al. (1992) Incidence and distribution of experimental metastases in mutant mice with defective organ microenvironments (genotypes Sl/Sld and W/Wv). Cancer Res 52:2304-9
Duerst, R E; Rose, D; Frantz, C N (1991) Complement depletion in vitro limits monoclonal antibody 6-19-dependent complement-mediated killing of tumor cells in bone marrow. Exp Hematol 19:863-7
Arguello, F; Baggs, R B; Eskenazi, A E et al. (1991) Vascular anatomy and organ-specific tumor growth as critical factors in the development of metastases and their distribution among organs. Int J Cancer 48:583-90
Arguello, F; Baggs, R B; Duerst, R E et al. (1990) Pathogenesis of vertebral metastasis and epidural spinal cord compression. Cancer 65:98-106
Frantz, C N; Ryan, D H; Cheung, N V et al. (1988) Sensitive detection of rare metastatic human neuroblastoma cells in bone marrow by two-color immunofluorescence and cell sorting. Prog Clin Biol Res 271:249-62
Erickson-Miller, C L; Abboud, C N; Stach, R W et al. (1988) Macrophage colony-stimulating factor in nerve growth factor preparations. J Neurosci Res 19:52-6
Arguello, F; Baggs, R B; Frantz, C N (1988) A murine model of experimental metastasis to bone and bone marrow. Cancer Res 48:6876-81
Ryan, D; Kossover, S; Mitchell, S et al. (1986) Subpopulations of common acute lymphoblastic leukemia antigen-positive lymphoid cells in normal bone marrow identified by hematopoietic differentiation antigens. Blood 68:417-25
Duerst, R E; Ryan, D H; Frantz, C N (1986) Variables affecting the killing of cultured human neuroblastoma cells with monoclonal antibody and complement. Cancer Res 46:3420-5

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