Pharmacological modulation of humoral immunity in a nonhuman primate model of AAV gene transfer for hemophilia B.

Molecular Therapy : the Journal of the American Society of Gene Therapy
F MingozziK A High

Abstract

Liver gene transfer for hemophilia B has shown very promising results in recent clinical studies. A potential complication of gene-based treatments for hemophilia and other inherited disorders, however, is the development of neutralizing antibodies (NAb) against the therapeutic transgene. The risk of developing NAb to the coagulation factor IX (F.IX) transgene product following adeno-associated virus (AAV)-mediated hepatic gene transfer for hemophilia is small but not absent, as formation of inhibitory antibodies to F.IX is observed in experimental animals following liver gene transfer. Thus, strategies to modulate antitransgene NAb responses are needed. Here, we used the anti-B cell monoclonal antibody rituximab (rtx) in combination with cyclosporine A (CsA) to eradicate anti-human F.IX NAb in rhesus macaques previously injected intravenously with AAV8 vectors expressing human F.IX. A short course of immunosuppression (IS) resulted in eradication of anti-F.IX NAb with restoration of plasma F.IX transgene product detection. In one animal, following IS anti-AAV6 antibodies also dropped below detection, allowing for successful AAV vector readministration and resulting in high levels (60% or normal) of F.IX transgene product in pl...Continue Reading

References

Dec 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·J P EvansK A High
Oct 23, 1997·Proceedings of the National Academy of Sciences of the United States of America·L WangI M Verma
Jun 9, 2001·The New England Journal of Medicine·D A RothUNKNOWN Factor VIII Transkaryotic Therapy Study Group
Sep 8, 2001·Molecular Therapy : the Journal of the American Society of Gene Therapy·P A FieldsK A High
May 3, 2003·The Journal of Clinical Investigation·Federico MingozziRoland W Herzog
Apr 29, 2006·Haemophilia : the Official Journal of the World Federation of Hemophilia·R A FoxC M Bennett
Jan 11, 2007·Haemophilia : the Official Journal of the World Federation of Hemophilia·J J FieldM A Blinder
Mar 21, 2007·Nature Medicine·Federico MingozziKatherine A High
Jul 7, 2007·British Journal of Haematology·Donna DiMichele
Feb 12, 2009·British Journal of Haematology·Johanna SvahnCarlo Dufour
Jul 16, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ou CaoRoland W Herzog
Feb 26, 2010·Haemophilia : the Official Journal of the World Federation of Hemophilia·H Chambost
Jun 16, 2010·Haemophilia : the Official Journal of the World Federation of Hemophilia·C BarnesP Monagle
Aug 4, 2010·The Journal of Experimental Medicine·Yenkel Grinberg-BleyerEliane Piaggio
Jan 20, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Amit C NathwaniAndrew M Davidoff
Feb 16, 2011·Proceedings of the National Academy of Sciences of the United States of America·Giridhara R JayandharanArun Srivastava
Mar 3, 2011·Haemophilia : the Official Journal of the World Federation of Hemophilia·G KamH J Ng
Apr 19, 2011·Nature Reviews. Genetics·Federico Mingozzi, Katherine A High
Apr 27, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Janka MátraiLuigi Naldini
May 12, 2011·Current Gene Therapy·Federico Mingozzi, Katherine A High
Jun 2, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Virginie MonteilhetCarole Masurier
Jun 4, 2011·Blood·Pasquale Pignatelli, Roberto Carnevale
Jun 18, 2011·Pediatric Blood & Cancer·Chikara OgimiTsutomu Oh-Ishi
Sep 8, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Marianna HöselHildegard Büning
Sep 29, 2011·Frontiers in Microbiology·Geoffrey L RogersRoland W Herzog
Dec 2, 2011·The New England Journal of Medicine·David SaadounDavid Klatzmann
Dec 14, 2011·The New England Journal of Medicine·Amit C NathwaniAndrew M Davidoff

❮ Previous
Next ❯

Citations

May 30, 2013·Molecular Therapy. Nucleic Acids·Hironori OkadaTakashi Okada
Feb 28, 2013·Human Gene Therapy Methods·Vedell Louis JeuneThomas Weber
Jul 19, 2013·Science Translational Medicine·Federico MingozziKatherine A High
Oct 10, 2013·EMBO Molecular Medicine·David M MarkusicRoland W Herzog
Jun 24, 2014·Molecular Therapy : the Journal of the American Society of Gene Therapy·Marinee K ChuahThierry VandenDriessche
Nov 3, 2015·Expert Opinion on Biological Therapy·Mark A BrimbleAndrew M Davidoff
Dec 18, 2013·Expert Opinion on Biological Therapy·Maria C ScimiaWalter J Koch
Jan 15, 2013·Translational Research : the Journal of Laboratory and Clinical Medicine·Manish R Patel, Robert A Kratzke
Nov 11, 2014·Human Gene Therapy·Sang-Oh HanDwight Koeberl
Jul 28, 2016·Current Opinion in Virology·Dongsheng Duan
Aug 16, 2016·Molecular Therapy. Methods & Clinical Development·Min Young LeeYehoash Raphael
Mar 1, 2018·Human Gene Therapy. Clinical Development·Jeff L EllsworthAlbert Seymour
Oct 24, 2018·The Journal of Clinical Investigation·Klaudia KurandaFederico Mingozzi
May 6, 2019·Clinical and Experimental Medicine·Majid LotfiniaMorteza Karimipoor
May 20, 2015·Expert Opinion on Biological Therapy·Longping V TseAravind Asokan
Aug 5, 2017·Frontiers in Pharmacology·Ruchita SelotGiridhara R Jayandharan
Nov 5, 2019·Journal of Tissue Engineering and Regenerative Medicine·Paula García-OlloquiBeatriz Pelacho
Jun 2, 2017·Journal of Inherited Metabolic Disease·Julien BaruteauPaul Gissen
Apr 5, 2018·Frontiers in Immunology·Moanaro BiswasRoland W Herzog
Apr 7, 2018·Human Gene Therapy. Clinical Development·Jeff L EllsworthAlbert Seymour
Dec 15, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jerry R MendellJacques P Tremblay
Dec 15, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Brian R LongBecky Schweighardt
Apr 11, 2021·Biological Reviews of the Cambridge Philosophical Society·Michael WhiteheadKeith Martin
Nov 14, 2020·Blood Reviews·Robert F SidonioStacy E Croteau
Jun 4, 2020·Molecular Therapy. Methods & Clinical Development·Benjamin J Samelson-JonesValder R Arruda
Jan 24, 2020·Molecular Therapy. Methods & Clinical Development·Ashley T Martino, David M Markusic
Jun 20, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Lindsey A GeorgeKatherine A High
Jun 7, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Maja van HeesKira Astakhova

❮ Previous
Next ❯

Methods Mentioned

BETA
protein replacement therapy
transfection
electrophoresis
PCR
flow cytometry
enzyme-linked immunosorbent assay

Software Mentioned

FlowJo
Prism
GraphPad

Related Concepts

Related Feeds

Cell-Type-Specific Viral Vectors (ASM)

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.

Cell-Type Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Cell-Type-Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.