A phase I clinical trial of systemically delivered NEMO binding domain peptide in dogs with spontaneous activated B-cell like diffuse large B-cell lymphoma.

Autor: Georges Habineza Ndikuyeze, Anita Gaurnier-Hausser, Reema Patel, Albert S Baldwin, Michael J May, Patrick Flood, Erika Krick, Kathleen J Propert, Nicola J Mason
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: PLoS ONE, Vol 9, Iss 5, p e95404 (2014)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0095404
Popis: Activated B-Cell (ABC) Diffuse Large B-Cell Lymphoma (DLBCL) is a common, aggressive and poorly chemoresponsive subtype of DLBCL, characterized by constitutive canonical NF-κB signaling. Inhibition of NF-κB signaling leads to apoptosis of ABC-DLBCL cell lines, suggesting targeted disruption of this pathway may have therapeutic relevance. The selective IKK inhibitor, NEMO Binding Domain (NBD) peptide effectively blocks constitutive NF-κB activity and induces apoptosis in ABC-DLBCL cells in vitro. Here we used a comparative approach to determine the safety and efficacy of systemic NBD peptide to inhibit constitutive NF-κB signaling in privately owned dogs with spontaneous newly diagnosed or relapsed ABC-like DLBCL. Malignant lymph nodes biopsies were taken before and twenty-four hours after peptide administration to determine biological effects. Intravenous administration of
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