Phase 2 clinical trial of a recombinant adeno-associated viral vector expressing α 1-antitrypsin: Interim results

Human Gene Therapy

Volumn 22, Issue 10, 2011, Pages 1239-1247

  Flotte, Terence R ^a   Trapnell, Bruce C ^b   Humphries, Margaret ^a   Carey, Brenna ^b   Calcedo, Roberto ^c   Rouhani, Farshid ^d   Campbell Thompson, Martha ^d   Yachnis, Anthony T ^d   Sandhaus, Robert A ^e   McElvaney, Noel G ^f   Mueller, Christian ^a   Messina, Louis M ^a   Wilson, James M ^c   Brantly, Mark ^d   Knop, David R ^g   Ye, Guo Jie ^g   Chulay, Jeffrey D ^g  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^b CINCINNATI CHILDREN'S HOSPITAL MEDICAL CENTER   (United States)

^c UNIVERSITY OF PENNSYLVANIA   (United States)

^d UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

^e DEPARTMENT OF MEDICINE   (United States)

^f BEAUMONT HOSPITAL   (Ireland)

^g APPLIED GENETIC TECHNOLOGIES CORPORATION   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOVIRUS VECTOR; ALPHA 1 ANTITRYPSIN; CREATINE KINASE; GAMMA INTERFERON; GLOBULIN; GLUCOSE;

ADENOVIRUS; ADULT; AGED; ALPHA 1 ANTITRYPSIN DEFICIENCY; ARTICLE; BACKACHE; CD8+ T LYMPHOCYTE; CLINICAL ARTICLE; CONNECTIVE TISSUE DISEASE; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CREATINE KINASE BLOOD LEVEL; DOSE RESPONSE; DRUG FEVER; DRUG INDUCED HEADACHE; DRUG SAFETY; ENZYME LINKED IMMUNOSORBENT ASSAY; ENZYME LINKED IMMUNOSPOT ASSAY; FEMALE; FLU LIKE SYNDROME; FURUNCULOSIS; GENE EXPRESSION; GENOME; HERPES SIMPLEX VIRUS; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; INJECTION SITE BLEEDING; INJECTION SITE CONTUSION; INJECTION SITE DISCOMFORT; INJECTION SITE ERYTHEMA; INJECTION SITE PAIN; MALE; MULTICENTER STUDY; MUSCLE SPASM; MUSCLE STRAIN; MYALGIA; NAUSEA; PHASE 2 CLINICAL TRIAL; PHLEBITIS; PROTEIN BLOOD LEVEL; PROTEIN TARGETING; SIDE EFFECT; SINUS HEADACHE; SKIN BLEEDING; T LYMPHOCYTE; THROAT IRRITATION; THRUSH; VIRAL GASTROENTERITIS; VIRAL GENE DELIVERY SYSTEM; VIRAL GENE THERAPY; VIRUS RECOMBINANT;

ALPHA 1-ANTITRYPSIN; ALPHA 1-ANTITRYPSIN DEFICIENCY; ANTIBODIES; CREATINE KINASE; DEPENDOVIRUS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG TOXICITY; ENZYME-LINKED IMMUNOSPOT ASSAY; GENE THERAPY; GENETIC VECTORS; HUMANS; IMMUNOPHENOTYPING; INJECTIONS, INTRAMUSCULAR; INTERFERON-GAMMA;

ADENO-ASSOCIATED VIRUS; SIMPLEXVIRUS;

EID: 80155145248     PISSN: 10430342     EISSN: 15577422     Source Type: Journal    
DOI: 10.1089/hum.2011.053     Document Type: Article

References (28)

1. Asokan, A., Conway, J.C., Phillips, J.L., et al. (2010). Reengineering a receptor footprint of adeno-associated virus enables selective and systemic gene transfer to muscle. Nat. Biotechnol. 28, 79-82.
2. Brantly, M.L., Wittes, J.T., Vogelmeier, C.F., et al. (1991). Use of a highly purified a1-antitrypsin standard to establish ranges for the common normal and deficient a1-antitrypsin phenotypes. Chest 100, 703-708.
3. Brantly, M.L., Spencer, L.T., Humphries, M., et al. (2006). Phase I trial of intramuscular injection of a recombinant adenoassociated virus serotype 2 a1-antitrypsin (AAT) vector in AAT-deficient adults. Hum. Gene Ther. 17, 1177-1186. (Pubitemid 44975135)
4. Brantly, M.L., Chulay, J.D., Wang, L., et al. (2009). Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy. Proc. Natl. Acad. Sci. U.S.A. 106, 16363-16368.
5. Chao, H., Liu, Y., Rabinowitz, J., et al. (2000). Several log increase in therapeutic transgene delivery by distinct adeno-associated viral serotype vectors. Mol. Ther. 2, 619-623.
6. Chulay, J.D., Ye, G.J., Thomas, D.L., et al. (2011). Preclinical evaluation of a recombinant adeno-associated virus vector expressing human a1-antitrypsin made using a recombinant herpes simplex virus production method. Hum. Gene Ther. 22, 155-165.
7. Conway, J.E., Rhys, C.M., Zolotukhin, I., et al. (1999). High-titer recombinant adeno-associated virus production utilizing a recombinant herpes simplex virus type I vector expressing AAV-2 Rep and Cap. Gene Ther. 6, 986-993. (Pubitemid 29295203)
8. De, B.P., Heguy, A., Hackett, N.R., et al. (2006). High levels of persistent expression of a1-antitrypsin mediated by the nonhuman primate serotype rh.10 adeno-associated virus despite preexisting immunity to common human adeno-associated viruses. Mol. Ther. 13, 67-76. (Pubitemid 41763484)
9. Gao, G.P., Alvira, M.R., Wang, L., et al. (2002). Novel adenoassociated viruses from rhesus monkeys as vectors for human gene therapy. Proc. Natl. Acad. Sci. U.S.A. 99, 11854-11859. (Pubitemid 34994488)
10. Halbert, C.L., Madtes, D.K., Vaughan, A.E., et al. (2010). Expression of human a1-antitrypsin in mice and dogs following AAV6 vector-mediated gene transfer to the lungs. Mol. Ther. 18, 1165-1172.
11. Kang, W., Wang, L., Harrell, H., et al. (2009). An efficient rHSVbased complementation system for the production of multiple rAAV vector serotypes. Gene Ther. 16, 229-239.
12. Liqun Wang, R., McLaughlin, T., Cossette, T., et al. (2009). Recombinant AAV serotype and capsid mutant comparison for pulmonary gene transfer of a1-antitrypsin using invasive and noninvasive delivery. Mol. Ther. 17, 81-87.
13. Lu, Y., Choi, Y.K., Campbell-Thompson, M., et al. (2006). Therapeutic level of functional human a1-antitrypsin (hAAT) secreted from murine muscle transduced by adeno-associated virus (rAAV1) vector. J. Gene Med. 8, 730-735.
14. Manno, C.S., Chew, A.J., Hutchison, S., et al. (2003). AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B. Blood 101, 2963-2972. (Pubitemid 36857981)
15. Manno, C.S., Pierce, G.F., Arruda, V.R., et al. (2006). Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nat. Med. 12, 342-347. (Pubitemid 43355084)
16. Poirier, A.E., Combee, L.A., Martino, A.T., and Flotte, T.R. (2004). Toxicology and biodistribution studies of a recombinant adeno-associated virus 2 (rAAV2) alpha-1 antitrypsin (AAT) vector. Mol. Ther. 9, S40.
17. Pulicherla, N., Shen, S., Yadav, S., et al. (2011). Engineering liverdetargeted AAV9 vectors for cardiac and musculoskeletal gene transfer. Mol. Ther. 19, 1070-1078.
18. Qiao, C., Zhang, W., Yuan, Z., et al. (2010). Adeno-associated virus serotype 6 capsid tyrosine-to-phenylalanine mutations improve gene transfer to skeletal muscle. Hum. Gene Ther. 21, 1343-1348.
19. Rabinowitz, J.E., Rolling, F., Li, C., et al. (2002). Cross-packaging of a single adeno-associated virus (AAV) type 2 vector genome into multiple AAV serotypes enables transduction with broad specificity. J. Virol. 76, 791-801. (Pubitemid 34033377)
20. Rodino-Klapac, L.R., Janssen, P.M., Montgomery, C.L., et al. (2007). A translational approach for limb vascular delivery of the micro-dystrophin gene without high volume or high pressure for treatment of Duchenne muscular dystrophy. J. Transl. Med. 5, 45.
21. Silverman, E.K., and Sandhaus, R.A. (2009). Clinical practice: a1-Antitrypsin deficiency. N. Engl. J. Med. 360, 2749-2757.
22. Song, S., Morgan, M., Ellis, T., et al. (1998). Sustained secretion of human a1-antitrypsin from murine muscle transduced with adeno-associated virus vectors. Proc. Natl. Acad. Sci. U.S.A. 95, 14384-14388. (Pubitemid 28549376)
23. Song, S., Scott-Jorgensen, M., Wang, J., et al. (2002). Intramuscular administration of recombinant adeno-associated virus 2 a1-antitrypsin (rAAV-SERPINA1) vectors in a nonhuman primate model: Safety and immunologic aspects. Mol. Ther. 6, 329-335. (Pubitemid 36305334)
24. Stroes, E.S., Nierman, M.C., Meulenberg, J.J., et al. (2008). Intramuscular administration of AAV1-lipoprotein lipase S447X lowers triglycerides in lipoprotein lipase-deficient patients. Arterioscler. Thromb. Vasc. Biol. 28, 2303-2304.
25. Thomas, D.L., Wang, L., Niamke, J., et al. (2009). Scalable recombinant adeno-associated virus production using recombinant herpes simplex virus type 1 coinfection of suspension-adapted mammalian cells. Hum. Gene Ther. 20, 861-870.
26. Toromanoff, A., Cherel, Y., Guilbaud, M., et al. (2008). Safety and efficacy of regional intravenous (r.i.) versus intramuscular (i.m.) delivery of rAAV1 and rAAV8 to nonhuman primate skeletal muscle. Mol. Ther. 16, 1291-1299. (Pubitemid 351866061)
27. Toromanoff, A., Adjali, O., Larcher, T., et al. (2010). Lack of immunotoxicity after regional intravenous (RI) delivery of rAAV to nonhuman primate skeletal muscle. Mol. Ther. 18, 151-160.
28. Xiao, W., Chirmule, N., Berta, S.C., et al. (1999). Gene therapy vectors based on adeno-associated virus type 1. J. Virol. 73, 3994-4003. (Pubitemid 29189844)