Previous studies, employing the murine system, have shown that mice with plasmacytomas develop a marked expansion of CD8+, T cells with cell surface Fc receptors (FcR). FcR are shed from the surface of FcR+T cells and become immunoglobulin-binding factors (IBF). IBF can bind to sIg on murine myeloma cells and can cause a down regulation of cell growth as well as immunoglobulin production. IBF act by selectively modulating signal transduction events with subsequent suppression of c- myc and immunoglobulin heavy and light chain gene transcription. Preliminary studies in patients with IgG-secreting myeloma have shown that CD16+ (FcGR III) cells are expanded in the peripheral blood. Soluble CD16 (sCD16) isolated from these cells can suppress the growth and Ig production by a human IgG producing cell line. In this application we propose to: 1) Enumerate the number, isotope specificity, and phenotype of FcR+ cells in patients with myeloma. We will correlate this data with clinical parameters accumulated in the myeloma patient data base. 2) Ascertain the frequency of patients producing soluble IBF and study the induction of, and structure and function of, patient IBF compared to normal controls. We will test patient IBF against autologous myeloma tumor cells in primary cultures as well as against cell lines. 3) Study the molecular mechanism whereby patient sCD16 modulates the growth and/or differentiation of human myeloma cells. These studies will provide new information and insight into the immunobiology of myeloma as well as establish the foundation for the development of new immunotherapeutic modalities for the treatment of myeloma and related B cell neoplasms.
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