Dana-Farber And Sanford-Burnham Institute License Flu-Targeting Antibodies
Article Date: 09 Feb 2010 - 0:00 PST
Dana-Farber Cancer Institute and the Sanford-Burnham Medical Research Institute have signed a license agreement with Genentech, a wholly owned member of the Roche group, and Roche, that grants the companies exclusive rights to manufacture, develop and market human monoclonal antibodies to treat and protect against group 1 influenza viruses. These viruses include the strains for the current seasonal and H1N1 influenzas. Genentech and Roche also have a non-exclusive right to manufacture, develop and market diagnostic tests for group 1 influenza.
The discovery of the antibodies was first reported by Wayne A. Marasco, MD, PhD, associate professor of medicine at Dana-Farber and Harvard Medical School; Robert Liddington, PhD, professor and director, Infectious and Inflammatory Disease Center at Sanford-Burnham; and Ruben Donis, PhD, chief of the Molecular Virology and Vaccines Branch at the Centers for Disease Control and Prevention, in Nature Structural and Molecular Biology in February 2009.
They demonstrated that the newly identified antibodies attach to the stem region of the viral proteins (hemagglutinin), rather than to the head region, the standard target of current influenza vaccines. Binding to the highly conserved stem region prevents changes in the protein that are necessary for viral entry into the host cell, thereby inhibiting further infection of host cells and the rise of escape mutants. Standard influenza vaccines that consist of an attenuated, or killed, virus typically stimulate antibodies against the protein's head. These vaccines are less effective as the head region is prone to change, leading to the rise of forms of the virus that can evade neutralizing antibodies.
Complete terms of the agreement are not public, but Dana-Farber and Sanford-Burnham will receive license fees and may receive milestone payments and royalties.
Source Dana-Farber Cancer Institute Sanford-Burnham Medical Research Institute
Al gelezen? (met dank aan perseazes, gepost op IV)
New Class of Monoclonal Antibodies against Severe Influenza: Prophylactic and Therapeutic Efficacy in Ferrets
Robert H. E. Friesen1*, Wouter Koudstaal1, Martin H. Koldijk1, Gerrit Jan Weverling1, Just P. J. Brakenhoff1, Peter J. Lenting1, Koert J. Stittelaar2, Albert D. M. E. Osterhaus2,3, Ronald Kompier1, Jaap Goudsmit1 1 Crucell Holland BV, Leiden, The Netherlands, 2 ViroClinics BV, Rotterdam, The Netherlands, 3 Department of Virology, ErasmusMC, Rotterdam, The Netherlands
Background: The urgent medical need for innovative approaches to control influenza is emphasized by the widespread resistance of circulating subtype H1N1 viruses to the leading antiviral drug oseltamivir, the pandemic threat posed by the occurrences of human infections with highly pathogenic avian H5N1 viruses, and indeed the evolving swine-origin H1N1 influenza pandemic. A recently discovered class of human monoclonal antibodies with the ability to neutralize a broad spectrum of influenza viruses (including H1, H2, H5, H6 and H9 subtypes) has the potential to prevent and treat influenza in humans. Here we report the latest efficacy data for a representative antibody of this novel class.
Methodology/Principal Findings: We evaluated the prophylactic and therapeutic efficacy of the human monoclonal antibody CR6261 against lethal challenge with the highly pathogenic avian H5N1 virus in ferrets, the optimal model of human influenza infection. Survival rates, clinically relevant disease signs such as changes in body weight and temperature, virus replication in lungs and upper respiratory tract, as well as macro- and microscopic pathology were investigated. Prophylactic administration of 30 and 10 mg/kg CR6261 prior to viral challenge completely prevented mortality, weight loss and reduced the amount of infectious virus in the lungs by more than 99.9%, abolished shedding of virus in pharyngeal secretions and largely prevented H5N1-induced lung pathology. When administered therapeutically 1 day after challenge, 30 mg/kg CR6261 prevented death in all animals and blunted disease, as evidenced by decreased weight loss and temperature rise, reduced lung viral loads and shedding, and less lung damage.
Conclusions/Significance: These data demonstrate the prophylactic and therapeutic efficacy of this new class of human monoclonal antibodies in a highly stringent and clinically relevant animal model of influenza and justify clinical development of this approach as intervention for both seasonal and pandemic influenza. Citation: Friesen RHE, Koudstaal W, Koldijk MH, Weverling GJ, Brakenhoff JPJ, et al. (2010) New Class of Monoclonal Antibodies against Severe Influenza: Prophylactic and Therapeutic Efficacy in Ferrets. PLoS ONE 5(2): e9106. doi:10.1371/journal.pone.0009106 Editor: Linqi Zhang, Tsinghua University, China
Received June 24, 2009; Accepted January 21, 2010; Published February 8, 2010 Copyright: _ 2010 Friesen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was funded by Crucell Holland BV (http://www.crucell.com). The funder had a role in study design, data analysis, decision to publish and preparation of the manuscript, but not in execution of the experiments and collection of the data. Competing Interests: The authors state that they have a financial interest. RF, WK, MK, GJW, JB, PL, RK, and JG are employees of Crucell Holland BV. KS and AO are employees of ViroClinics BV. AO is furthermore an employee of the ErasmusMC, Rotterdam.
Markt vandaag
