Publications [#140374] of John H Sampson

Papers Published

1. PE Fecci, AE Sweeney, PM Grossi, SK Nair, CA Learn, DA Mitchell, X Cui, TJ Cummings, DD Bigner, E Gilboa, JH Sampson, Systemic anti-CD25 monoclonal antibody administration safely enhances immunity in murine glioma without eliminating regulatory T cells., Clinical cancer research : an official journal of the American Association for Cancer Research, United States, vol. 12 no. 14 Pt 1 (July, 2006), pp. 4294-305, ISSN 1078-0432
   (last updated on 2007/12/20)

   Abstract:
   PURPOSE: Elevated proportions of regulatory T cells (T(reg)) are present in patients with a variety of cancers, including malignant glioma, yet recapitulative murine models are wanting. We therefore examined T(regs) in mice bearing malignant glioma and evaluated anti-CD25 as an immunotherapeutic adjunct. EXPERIMENTAL DESIGN: CD4+CD25+Foxp3+GITR+ T(regs) were quantified in the peripheral blood, spleens, cervical lymph nodes, and bone marrow of mice bearing malignant glioma. The capacities for systemic anti-CD25 therapy to deplete T(regs), enhance lymphocyte function, and generate antiglioma CTL responses were assessed. Lastly, survival and experimental allergic encephalitis risks were evaluated when anti-CD25 was combined with a dendritic cell-based immunization targeting shared tumor and central nervous system antigens. RESULTS: Similar to patients with malignant glioma, glioma-bearing mice show a CD4 lymphopenia. Additionally, CD4+CD25+Foxp3+GITR+ T(regs) represent an increased fraction of the remaining peripheral blood CD4+ T cells, despite themselves being reduced in number. Similar trends are observed in cervical lymph node and spleen, but not in bone marrow. Systemic anti-CD25 administration hinders detection of CD25+ cells but fails to completely eliminate T(regs), reducing their number only moderately, yet eliminating their suppressive function. This elimination of T(reg) function permits enhanced lymphocyte proliferative and IFN-gamma responses and up to 80% specific lysis of glioma cell targets in vitro. When combined with dendritic cell immunization, anti-CD25 elicits tumor rejection in 100% of challenged mice without precipitating experimental allergic encephalitis. CONCLUSIONS: Systemic anti-CD25 administration does not entirely eliminate T(regs) but does prevent T(reg) function. This leads to safe enhancement of tumor immunity in a murine glioma model that recapitulates the tumor-induced changes to the CD4 and T(reg) compartments seen in patients with malignant glioma.

   Keywords:
   Animals • Antibodies, Monoclonal • Antigens, CD4 • Bone Marrow Cells • Brain Neoplasms • Cell Line, Tumor • Dendritic Cells • Flow Cytometry • Glioma • Immunotherapy • Interferon Type II • Interleukin-2 Receptor alpha Subunit • Lymphocytes • Mice • T-Lymphocytes • T-Lymphocytes, Regulatory • biosynthesis • biosynthesis* • chemistry • chemistry* • metabolism • metabolism* • methods* • therapy*