By a News Reporter-Staff News Editor at Clinical Trials Week -- Data detailed on Biotechnology have been presented. According to news reporting from Lubbock, Texas, by NewsRx journalists, research stated, "Neuroblastoma (NB) is the most common extracranial solid tumor in children. Combining passive immunotherapy with an antibody to the disialoganglioside GD2 (ch14.18/SP2/0) and cytokines with 13-cis-retinoic acid for post-myeloablative maintenance therapy increased survival in high-risk NB, but the overall prognosis for these children is still in need of improvement."
The news correspondents obtained a quote from the research from the Texas Tech University School of Medicine, "Fenretinide (4-HPR) is a synthetic retinoid that has shown clinical activity in recurrent NB and is cytotoxic to a variety of cancer cells, in part via the accumulation of dihydroceramides, which are precursors of GD2. We investigated the effect of 4-HPR on CHO-derived, ch14.18-mediated anti-NB effector functions, complement-dependent cytotoxicity (CDC), and antibody-dependent and antibody-independent cellular cytotoxicity (ADCC and AICC, respectively). Here, we demonstrate for the first time that pretreatment of fenretinide-resistant NB cells with 4-HPR significantly enhanced ch14.18/CHO-mediated CDC and ADCC and AICC by both human natural killer cells and peripheral blood mononuclear cells. Treatment with 4-HPR increased GD2 and death receptor (DR) expression in resistant NB cells and induced an enhanced granzyme B and perforin production by effector cells. Blocking of ganglioside synthesis with a glucosylceramide synthase inhibitor abrogated the increased ADCC response but had no effect on the AICC, indicating that GD2 induced by 4-HPR mediates the sensitization of NB cells for ADCC. We also showed that 4-HPR induced increased GD2 and DR expression in a resistant NB xenograft model that was associated with an increased ADCC and AICC response using explanted tumor target cells from 4-HPR-treated mice."
According to the news reporters, the research concluded: "In summary, these findings provide an important baseline for the combination of 4-HPR and passive immunotherapy with ch14.18/CHO in future clinical trials for high-risk NB patients."
For more information on this research see: Fenretinide sensitizes multidrug-resistant human neuroblastoma cells to antibody-independent and ch14.18-mediated NK cell cytotoxicity. Journal of Molecular Medicine, 2013;91(4):459-72. Journal of Molecular Medicine can be contacted at: Springer, 233 Spring Street, New York, NY 10013, USA. (Springer - www.springer.com; Journal of Molecular Medicine - www.springerlink.com/content/0946-2716/)
Our news journalists report that additional information may be obtained by contacting A. Shibina, Cancer Center, Texas Technical University Health Sciences Center School of Medicine, Lubbock, TX, United States. Additional authors for this research include D. Seidel, S.S. Somanchi, D.A. Lee, A. Stermann, B.J. Maurer, H.N. Lode, C.P. Reynolds and N. Huebener (see also technology.html">Biotechnology).
Publisher contact information for the Journal of Molecular Medicine is: Springer, 233 Spring Street, New York, NY 10013, USA.
Keywords for this news article include: Antibodies, Biotechnology, Texas, Lubbock, Alkenes, Oncology, Polyenes, Terpenes, Retinoids, Hematology, Immunology, Pediatrics, Fenretinide, Cyclohexanes, Cyclohexenes, Hydrocarbons, United States, Immunotherapy, Neuroblastoma, Blood Proteins, Cycloparaffins, Drug Resistance, Immunoglobulins, Immunomodulation.
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