The Impact of Pre-existing Immunity on the Non-clinical Pharmacodynamics of AAV5-Based Gene Therapy

Molecular Therapy Methods and Clinical Development

Volumn 13, Issue , 2019, Pages 440-452

  Long, Brian R ^a   Sandza, Krystal ^a   Holcomb, Jennifer ^a   Crockett, Lucy ^a   Hayes, Gregory M ^a   Arens, Jeremy ^a   Fonck, Carlos ^a   Tsuruda, Laurie S ^a   Schweighardt, Becky ^a   O'Neill, Charles A ^a   Zoog, Stephen ^a   Vettermann, Christian ^a  

^a BIOMARIN PHARMACEUTICAL INC   (United States)

Author keywords

AAV; cynomolgus monkey; enrollment criteria; FVIII; gene therapy; hemophilia; immunogenicity; pharmacodynamics; total antibody; transduction inhibition

Indexed keywords

NEUTRALIZING ANTIBODY; VALOCTOCOGENE ROXAPARVOVEC; VIRUS ANTIBODY;

ADENO ASSOCIATED VIRUS 5; ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTIBODY BLOOD LEVEL; ANTIBODY TITER; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG BLOOD LEVEL; EVALUATION STUDY; GENE VECTOR; HEMOPHILIA; IMMUNITY; MACACA FASCICULARIS; MAXIMUM CONCENTRATION; NONHUMAN; PHARMACODYNAMICS; PLASMA FACTOR; PRIORITY JOURNAL; TREATMENT RESPONSE; VIRAL GENE DELIVERY SYSTEM; VIRAL GENE THERAPY;

EID: 85065130237     PISSN: None     EISSN: 23290501     Source Type: Journal    
DOI: 10.1016/j.omtm.2019.03.006     Document Type: Article

References (41)

1. Flotte, T.R., Carter, B.J., Adeno-associated virus vectors for gene therapy. Gene Ther. 2 (1995), 357–362.
2. Nathwani, A.C., Rosales, C., McIntosh, J., Rastegarlari, G., Nathwani, D., Raj, D., Nawathe, S., Waddington, S.N., Bronson, R., Jackson, S., et al. Long-term safety and efficacy following systemic administration of a self-complementary AAV vector encoding human FIX pseudotyped with serotype 5 and 8 capsid proteins. Mol. Ther. 19 (2011), 876–885.
3. Manno, C.S., Pierce, G.F., Arruda, V.R., Glader, B., Ragni, M., Rasko, J.J., Ozelo, M.C., Hoots, K., Blatt, P., Konkle, B., et al. Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nat. Med. 12 (2006), 342–347.
4. Boutin, S., Monteilhet, V., Veron, P., Leborgne, C., Benveniste, O., Montus, M.F., Masurier, C., Prevalence of serum IgG and neutralizing factors against adeno-associated virus (AAV)types 1, 2, 5, 6, 8, and 9 in the healthy population: implications for gene therapy using AAV vectors. Hum. Gene Ther. 21 (2010), 704–712.
5. Calcedo, R., Vandenberghe, L.H., Gao, G., Lin, J., Wilson, J.M., Worldwide epidemiology of neutralizing antibodies to adeno-associated viruses. J. Infect. Dis. 199 (2009), 381–390.
6. Liu, Q., Huang, W., Zhang, H., Wang, Y., Zhao, J., Song, A., Xie, H., Zhao, C., Gao, D., Wang, Y., Neutralizing antibodies against AAV2, AAV5 and AAV8 in healthy and HIV-1-infected subjects in China: implications for gene therapy using AAV vectors. Gene Ther. 21 (2014), 732–738.
7. Li, C., Narkbunnam, N., Samulski, R.J., Asokan, A., Hu, G., Jacobson, L.J., Manco-Johnson, M.J., Monahan, P.E., Joint Outcome Study Investigators. Neutralizing antibodies against adeno-associated virus examined prospectively in pediatric patients with hemophilia. Gene Ther. 19 (2012), 288–294.
8. Gouw, S.C., van der Bom, J.G., Marijke van den Berg, H., Treatment-related risk factors of inhibitor development in previously untreated patients with hemophilia A: the CANAL cohort study. Blood 109 (2007), 4648–4654.
9. Masat, E., Pavani, G., Mingozzi, F., Humoral immunity to AAV vectors in gene therapy: challenges and potential solutions. Discov. Med. 15 (2013), 379–389.
10. Calcedo, R., Wilson, J.M., AAV natural infection induces broad cross-neutralizing antibody responses to multiple AAV serotypes in chimpanzees. Hum. Gene Ther. Clin. Dev. 27 (2016), 79–82.
11. Callan, M.B., Haskins, M.E., Wang, P., Zhou, S., High, K.A., Arruda, V.R., Successful phenotype improvement following gene therapy for severe hemophilia A in privately owned dogs. PLoS ONE, 11, 2016, e0151800.
12. Corden, A., Handelman, B., Yin, H., Cotrim, A., Alevizos, I., Chiorini, J.A., Neutralizing antibodies against adeno-associated viruses in Sjögren's patients: implications for gene therapy. Gene Ther. 24 (2017), 241–244.
13. Louis Jeune, V., Joergensen, J.A., Hajjar, R.J., Weber, T., Pre-existing anti-adeno-associated virus antibodies as a challenge in AAV gene therapy. Hum. Gene Ther. Methods 24 (2013), 59–67.
14. Fu, H., Meadows, A.S., Pineda, R.J., Kunkler, K.L., Truxal, K.V., McBride, K.L., Flanigan, K.M., McCarty, D.M., Differential prevalence of antibodies against adeno-associated virus in healthy children and patients with mucopolysaccharidosis III: perspective for AAV-mediated gene therapy. Hum. Gene Ther. Clin. Dev. 28 (2017), 187–196.
15. Mimuro, J., Mizukami, H., Shima, M., Matsushita, T., Taki, M., Muto, S., Higasa, S., Sakai, M., Ohmori, T., Madoiwa, S., et al. The prevalence of neutralizing antibodies against adeno-associated virus capsids is reduced in young Japanese individuals. J. Med. Virol. 86 (2014), 1990–1997.
16. Falese, L., Sandza, K., Yates, B., Triffault, S., Gangar, S., Long, B., Tsuruda, L., Carter, B., Vettermann, C., Zoog, S.J., Fong, S., Strategy to detect pre-existing immunity to AAV gene therapy. Gene Ther. 24 (2017), 768–778.
17. Berry, G., Murlidharan, G., Asokan, A., Modulation of intracellular calcium enhances AAV transduction in the CNS. Mol. Ther., 24, 2016, S14.
18. Hirosue, S., Senn, K., Clément, N., Nonnenmacher, M., Gigout, L., Linden, R.M., Weber, T., Effect of inhibition of dynein function and microtubule-altering drugs on AAV2 transduction. Virology 367 (2007), 10–18.
19. Virella-Lowell, I., Poirier, A., Chesnut, K.A., Brantly, M., Flotte, T.R., Inhibition of recombinant adeno-associated virus (rAAV)transduction by bronchial secretions from cystic fibrosis patients. Gene Ther. 7 (2000), 1783–1789.
20. Nonnenmacher, M., Weber, T., Intracellular transport of recombinant adeno-associated virus vectors. Gene Ther. 19 (2012), 649–658.
21. Srivastava, A., Brewer, A.K., Mauser-Bunschoten, E.P., Key, N.S., Kitchen, S., Llinas, A., Ludlam, C.A., Mahlangu, J.N., Mulder, K., Poon, M.C., Street, A., Treatment Guidelines Working Group on Behalf of The World Federation Of Hemophilia. Guidelines for the management of hemophilia. Haemophilia 19 (2013), e1–e47.
22. McIntosh, J., Lenting, P.J., Rosales, C., Lee, D., Rabbanian, S., Raj, D., Patel, N., Tuddenham, E.G., Christophe, O.D., McVey, J.H., et al. Therapeutic levels of FVIII following a single peripheral vein administration of rAAV vector encoding a novel human factor VIII variant. Blood 121 (2013), 3335–3344.
23. Chiorini, J.A., Kim, F., Yang, L., Kotin, R.M., Cloning and characterization of adeno-associated virus type 5. J. Virol. 73 (1999), 1309–1319.
24. National Library of Medicine. Gene therapy study in severe haemophilia A patients. 2015 https://clinicaltrials.gov/ct2/show/NCT02576795.
25. Weinberg, M.S., Nicolson, S., Bhatt, A.P., McLendon, M., Li, C., Samulski, R.J., Recombinant adeno-associated virus utilizes cell-specific infectious entry mechanisms. J. Virol. 88 (2014), 12472–12484.
26. Davidoff, A.M., Gray, J.T., Ng, C.Y., Zhang, Y., Zhou, J., Spence, Y., Bakar, Y., Nathwani, A.C., Comparison of the ability of adeno-associated viral vectors pseudotyped with serotype 2, 5, and 8 capsid proteins to mediate efficient transduction of the liver in murine and nonhuman primate models. Mol. Ther. 11 (2005), 875–888.
27. Jiang, H., Couto, L.B., Patarroyo-White, S., Liu, T., Nagy, D., Vargas, J.A., Zhou, S., Scallan, C.D., Sommer, J., Vijay, S., et al. Effects of transient immunosuppression on adenoassociated, virus-mediated, liver-directed gene transfer in rhesus macaques and implications for human gene therapy. Blood 108 (2006), 3321–3328.
28. Nathwani, A.C., Gray, J.T., Ng, C.Y., Zhou, J., Spence, Y., Waddington, S.N., Tuddenham, E.G., Kemball-Cook, G., McIntosh, J., Boon-Spijker, M., et al. Self-complementary adeno-associated virus vectors containing a novel liver-specific human factor IX expression cassette enable highly efficient transduction of murine and nonhuman primate liver. Blood 107 (2006), 2653–2661.
29. Nathwani, A.C., Gray, J.T., McIntosh, J., Ng, C.Y., Zhou, J., Spence, Y., Cochrane, M., Gray, E., Tuddenham, E.G., Davidoff, A.M., Safe and efficient transduction of the liver after peripheral vein infusion of self-complementary AAV vector results in stable therapeutic expression of human FIX in nonhuman primates. Blood 109 (2007), 1414–1421.
30. George, L.A., Sullivan, S.K., Giermasz, A., Rasko, J.E.J., Samelson-Jones, B.J., Ducore, J., Cuker, A., Sullivan, L.M., Majumdar, S., Teitel, J., et al. Hemophilia B gene therapy with a high-specific-activity factor IX variant. N. Engl. J. Med. 377 (2017), 2215–2227.
31. Arbetman, A.E., Lochrie, M., Zhou, S., Wellman, J., Scallan, C., Doroudchi, M.M., Randlev, B., Patarroyo-White, S., Liu, T., Smith, P., et al. Novel caprine adeno-associated virus (AAV)capsid (AAV-Go.1)is closely related to the primate AAV-5 and has unique tropism and neutralization properties. J. Virol. 79 (2005), 15238–15245.
32. Gao, G., Vandenberghe, L.H., Alvira, M.R., Lu, Y., Calcedo, R., Zhou, X., Wilson, J.M., Clades of Adeno-associated viruses are widely disseminated in human tissues. J. Virol. 78 (2004), 6381–6388.
33. Rangarajan, S., Walsh, L., Lester, W., Perry, D., Madan, B., Laffan, M., Yu, H., Vettermann, C., Pierce, G.F., Wong, W.Y., Pasi, K.J., AAV5-factor VIII gene transfer in severe hemophilia A. N. Engl. J. Med. 377 (2017), 2519–2530.
34. Parenky, A., Myler, H., Amaravadi, L., Bechtold-Peters, K., Rosenberg, A., Kirshner, S., Quarmby, V., New FDA draft guidance on immunogenicity. AAPS J. 16 (2014), 499–503.
35. Food and Drug Administration. Assay development and validation for immunogenicity testing of therapeutic protein products; Guidance for Industry; Availability. Fed. Regist., 81, 2016, 24106.
36. Food and Drug Administration. Immunogenicity assessment for therapeutic protein products. 2014 https://www.fda.gov/downloads/drugs/guidances/ucm338856.pdf.
37. Wu, Z., Miller, E., Agbandje-McKenna, M., Samulski, R.J., Alpha2,3 and alpha2,6 N-linked sialic acids facilitate efficient binding and transduction by adeno-associated virus types 1 and 6. J. Virol. 80 (2006), 9093–9103.
38. Wang, M., Sun, J., Crosby, A., Woodard, K., Hirsch, M.L., Samulski, R.J., Li, C., Direct interaction of human serum proteins with AAV virions to enhance AAV transduction: immediate impact on clinical applications. Gene Ther. 24 (2017), 49–59.
39. Ferrari, F.K., Samulski, T., Shenk, T., Samulski, R.J., Second-strand synthesis is a rate-limiting step for efficient transduction by recombinant adeno-associated virus vectors. J. Virol. 70 (1996), 3227–3234.
40. Nathwani, A.C., Tuddenham, E.G., Rangarajan, S., Rosales, C., McIntosh, J., Linch, D.C., Chowdary, P., Riddell, A., Pie, A.J., Harrington, C., et al. Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N. Engl. J. Med. 365 (2011), 2357–2365.
41. National Research Council (US)Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals. 2011, National Academies Press, Washington, DC.