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Immunologic Research
Erschienen in: Immunologic Research 1-3/2009

01.07.2009

Hematopoietic stem cell gene therapy for adenosine deaminase deficient-SCID

verfasst von: Alessandro Aiuti, Immacolata Brigida, Francesca Ferrua, Barbara Cappelli, Robert Chiesa, Sarah Marktel, Maria-Grazia Roncarolo

Erschienen in: Immunologic Research | Ausgabe 1-3/2009

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Abstract

Gene therapy is a highly attractive strategy for many types of inherited disorders of the immune system. Adenosine deaminase (ADA) deficient-severe combined immunodeficiency (SCID) has been the target of several clinical trials based on the use of hematopoietic stem/progenitor cells engineered with retroviral vectors. The introduction of a low intensity conditioning regimen has been a crucial factor in achieving stable engrafment of hematopoietic stem cells and therapeutic levels of ADA-expressing cells. Recent studies have demonstrated that gene therapy for ADA-SCID has favorable safety profile and is effective in restoring normal purine metabolism and immune functions. Stem cell gene therapy combined with appropriate conditioning regimens might be extended to other genetic disorders of the hematopoietic system.
Literatur
1.
Bordignon C, Roncarolo MG. Therapeutic applications for hematopoietic stem cell gene transfer. Nat Immunol. 2002;3:318–21.PubMedCrossRef
2.
Fischer A, Le Deist F, Hacein-Bey-Abina S, Andre-Schmutz I, Basile Gde S, de Villartay JP, et al. Severe combined immunodeficiency. A model disease for molecular immunology and therapy. Immunol Rev. 2005;203:98–109.PubMedCrossRef
3.
Kohn DB. Gene therapy for childhood immunological diseases. Bone Marrow Transplant. 2008;41:199–205.PubMedCrossRef
4.
Aiuti A, Ficara F, Cattaneo F, Bordignon C, Roncarolo MG. Gene therapy for adenosine deaminase deficiency. Curr Opin Allergy Clin Immunol. 2003;3:461–6.PubMedCrossRef
5.
Aiuti A, Bachoud-Levi AC, Blesch A, Brenner MK, Cattaneo F, Chiocca EA, et al. Progress and prospects: gene therapy clinical trials (part 2). Gene Ther. 2007;14:1555–63.PubMedCrossRef
6.
Hirschorn R, Candotti F. Immunodeficiency due to defects of purine metabolism. In: Ochs H, Smith C, Puck J, editors. Primary immunodeficiency diseases. Oxford: Oxford University Press; 2006. p. 169–96.
7.
Hershfield MS. Adenosine deaminase deficiency: clinical expression, molecular basis, and therapy. Semin Hematol. 1998;35:291–8.PubMed
8.
Booth C, Hershfield M, Notarangelo L, Buckley R, Hoenig M, Mahlaoui N, et al. Management options for adenosine deaminase deficiency; proceedings of the EBMT satellite workshop (Hamburg, March 2006). Clin immunol. 2007;123:139–47.PubMedCrossRef
9.
Honig M, Albert MH, Schulz A, Sparber-Sauer M, Schutz C, Belohradsky B, et al. Patients with adenosine deaminase deficiency surviving after hematopoietic stem cell transplantation are at high risk of CNS complications. Blood. 2006;109:3595–602.PubMedCrossRef
10.
Ferrari G, Rossini S, Giavazzi R, Maggioni D, Nobili N, Soldati M, et al. An in vivo model of somatic cell gene therapy for human severe combined immunodeficiency. Science. 1991;251:1363–6.PubMedCrossRef
11.
Baum C, Kustikova O, Modlich U, Li Z, Fehse B. Mutagenesis and oncogenesis by chromosomal insertion of gene transfer vectors. Hum Gene Ther. 2006;17:253–63.PubMedCrossRef
12.
Ott MG, Schmidt M, Schwarzwaelder K, Stein S, Siler U, Koehl U, et al. Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1. Nat Med. 2006;12:401–9.PubMedCrossRef
13.
Hacein-Bey-Abina S, Garrigue A, Wang GP, Soulier J, Lim A, Morillon E, et al. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J Clin Invest. 2008;118:3132–42.PubMedCrossRef
14.
Howe SJ, Mansour MR, Schwarzwaelder K, Bartholomae C, Hubank M, Kempski H, et al. Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. J Clin Invest. 2008;118:3143–50.PubMedCrossRef
15.
Aiuti A, Cassani B, Andolfi G, Mirolo M, Biasco L, Recchia A, et al. Multilineage hematopoietic reconstitution without clonal selection in ADA-SCID patients treated with stem cell gene therapy. J Clin Invest. 2007;117:2233–40.PubMedCrossRef
16.
Engel BC, Podsakoff GM, Ireland JL, Smogorzewska EM, Carbonaro DA, Wilson K, et al. Prolonged pancytopenia in a gene therapy patient with ADA-deficient SCID and trisomy 8 mosaicism: a case report. Blood. 2007;109:503–6.PubMedCrossRef
17.
Blaese RM, Culver KW, Miller AD, Carter CS, Fleisher T, Clerici M, et al. T lymphocyte-directed gene therapy for ADA-SCID: initial trial results after 4 years. Science. 1995;270:475–80.PubMedCrossRef
18.
Bordignon C, Notarangelo LD, Nobili N, Ferrari G, Casorati G, Panina P, et al. Gene therapy in peripheral blood lymphocytes and bone marrow for ADA-immunodeficient patients. Science. 1995;270:470–5.PubMedCrossRef
19.
Onodera M, Ariga T, Kawamura N, Kobayashi I, Ohtsu M, Yamada M, et al. Successful peripheral T-lymphocyte-directed gene transfer for a patient with severe combined immune deficiency caused by adenosine deaminase deficiency. Blood. 1998;91:30–6.PubMed
20.
Muul LM, Tuschong LM, Soenen SL, Jagadeesh GJ, Ramsey WJ, Long Z, et al. Persistence and expression of the adenosine deaminase gene for 12 years and immune reaction to gene transfer components: long-term results of the first clinical gene therapy trial. Blood. 2003;101:2563–9.PubMedCrossRef
21.
Aiuti A, Vai S, Mortellaro A, Casorati G, Ficara F, Andolfi G, et al. Immune reconstitution in ADA-SCID after PBL gene therapy and discontinuation of enzyme replacement. Nat Med. 2002;8:423–5.PubMedCrossRef
22.
Kohn DB, Hershfield MS, Carbonaro D, Shigeoka A, Brooks J, Smogorzewska EM, et al. T lymphocytes with a normal ADA gene accumulate after transplantation of transduced autologous umbilical cord blood CD34 + cells in ADA-deficient SCID neonates. Nat Med. 1998;4:775–80.PubMedCrossRef
23.
Kohn DB, Weinberg KI, Nolta JA, Heiss LN, Lenarsky C, Crooks GM, et al. Engraftment of gene-modified umbilical cord blood cells in neonates with adenosine deaminase deficiency. Nat Med. 1995;1:1017–23.PubMedCrossRef
24.
Schmidt M, Carbonaro DA, Speckmann C, Wissler M, Bohnsack J, Elder M, et al. Clonality analysis after retroviral-mediated gene transfer to CD34+ cells from the cord blood of ADA-deficient SCID neonates. Nat Med. 2003;9:463–8.PubMedCrossRef
25.
Haddad E, Landais P, Friedrich W, Gerritsen B, Cavazzana CM, Morgan G, et al. Long-term immune reconstitution and outcome after HLA-nonidentical T-cell-depleted bone marrow transplantation for severe combined immunodeficiency: a European retrospective study of 116 patients. Blood. 1998;91:3646–53.PubMed
26.
Huhn RD, Tisdale JF, Agricola B, Metzger ME, Donahue RE, Dunbar CE. Retroviral marking and transplantation of rhesus hematopoietic cells by nonmyeloablative conditioning. Hum Gene Ther. 1999;10:1783–90.PubMedCrossRef
27.
Rosenzweig M, MacVittie TJ, Harper D, Hempel D, Glickman RL, Johnson RP, et al. Efficient and durable gene marking of hematopoietic progenitor cells in nonhuman primates after nonablative conditioning. Blood. 1999;94:2271–86.PubMed
28.
Slavin S, Aker M, Shapira MY, Panigrahi S, Gabriel C, Or R. Non-myeloablative stem cell transplantation for the treatment of cancer and life-threatening non-malignant disorders; past accomplishments and future goals. Transfus Apher Sci. 2002;27:159–66.PubMedCrossRef
29.
Kuramoto K, Follman D, Hematti P, Sellers S, Laukkanen MO, Seggewiss R, et al. The impact of low-dose busulfan on clonal dynamics in nonhuman primates. Blood. 2004;104:1273–80.PubMedCrossRef
30.
Bolinger AM, Zangwill AB, Slattery JT, Glidden D, DeSantes K, Heyn L, et al. An evaluation of engraftment, toxicity and busulfan concentration in children receiving bone marrow transplantation for leukemia or genetic disease. Bone Marrow Transplant. 2000;25:925–30.PubMedCrossRef
31.
Dando JS, Aiuti A, Deola S, Ficara F, Bordignon C. Optimisation of retroviral supernatant production conditions for the genetic modification of human CD34+ cells. J Gene Med. 2001;3:219–27.PubMedCrossRef
32.
Williams DA. Retroviral-fibronectin interactions in transduction of mammalian cells. Ann N Y Acad Sci. 1999;872:109–13. discussion 113–104.PubMedCrossRef
33.
Aiuti A, Slavin S, Aker M, Ficara F, Deola S, Mortellaro A, et al. Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning. Science. 2002;296:2410–3.PubMedCrossRef
34.
Ficara F, Superchi DB, Hernandez RJ, Mocchetti C, Carballido-Perrig N, Andolfi G, et al. IL–3 or IL–7 increases ex vivo gene transfer efficiency in ADA-SCID BM CD34+ cells while maintaining in vivo lymphoid potential. Mol Ther. 2004;10:1096–108.PubMedCrossRef
35.
Aiuti A, Cattaneo F, Galimberti S, Benninghoff U, Cassani B, Callegaro L, et al. Long-term safety and efficacy of gene therapy for adenosine deaminase (ADA)-deficient severe combined immunodeficiency. New Engl J Med. 2009;360:447–58.
36.
Cassani B, Mirolo M, Cattaneo F, Benninghoff U, Hershfield M, Carlucci F, et al. Altered intracellular and extracellular signaling leads to impaired T-cell functions in ADA-SCID patients. Blood. 2008;111:4209–19.PubMedCrossRef
37.
Gaspar HB, Bjorkegren E, Parsley K, Gilmour KC, King D, Sinclair J, et al. Successful reconstitution of immunity in ADA-SCID by stem cell gene therapy following cessation of PEG-ADA and use of mild preconditioning. Mol Ther. 2006;14:505–13.PubMedCrossRef
38.
Otsu M, Nakajima M, Kida M, Maeyama Y, Toita N, Hatano N, et al. Stem cell gene therapy with no pre-conditioning for the ADA-deficiency patients leads to generalized detoxification and delayed, but steady hematological reconstitution. Mol Ther. 2006;13:S418. (Abstract).
39.
Sokolic R, Podsakoff G, Muul L, Engel B, Jagadeesh J, Garabedian E, et al. Myelosupression and withdrawal of PEG-ADA lead to superior results after gene therapy for adenosine deaminase deficiency (ADA-SCID). Mol Ther. 2008;16:S111. (Abstract).
40.
Dave UP, Jenkins NA, Copeland NG. Gene therapy insertional mutagenesis insights. Science. 2004;303:333.PubMedCrossRef
41.
Shou Y, Ma Z, Lu T, Sorrentino BP. Unique risk factors for insertional mutagenesis in a mouse model of XSCID gene therapy. Proc Natl Acad Sci USA. 2006;103:11730–5.PubMedCrossRef
42.
Follenzi A, Ailles LE, Bakovic S, Geuna M, Naldini L. Gene transfer by lentiviral vectors is limited by nuclear translocation and rescued by HIV-1 pol sequences. Nat Genet. 2000;25:217–22.PubMedCrossRef
43.
Mortellaro A, Hernandez RJ, Guerrini MM, Carlucci F, Tabucchi A, Ponzoni M, et al. Ex vivo gene therapy with lentiviral vectors rescues adenosine deaminase (ADA)-deficient mice and corrects their immune and metabolic defects. Blood. 2006;108:2979–88.
44.
De Palma M, Montini E, de Sio FR, Benedicenti F, Gentile A, Medico E, et al. Promoter trapping reveals significant differences in integration site selection between MLV and HIV vectors in primary hematopoietic cells. Blood. 2005;105:2307–15.PubMedCrossRef
45.
Montini E, Cesana D, Schmidt M, Sanvito F, Ponzoni M, Bartholomae C, et al. Hematopoietic stem cell gene transfer in a tumor-prone mouse model uncovers low genotoxicity of lentiviral vector integration. Nat Biotechnol. 2006;24:687–96.PubMedCrossRef
46.
Galy A, Roncarolo MG, Thrasher AJ. Development of lentiviral gene therapy for Wiskott Aldrich syndrome. Expert Opin Biol Ther. 2008;8:181–90.PubMedCrossRef
47.
Dupré L, Marangoni F, Scaramuzza S, Trifari S, Hernandez RJ, Aiuti A, et al. Efficacy of gene therapy for Wiskott-Aldrich syndrome using a WAS promoter/cDNA-containing lentiviral vector and nonlethal irradiation. Hum Gene Ther. 2006;17:303–13.
Metadaten
Titel
Hematopoietic stem cell gene therapy for adenosine deaminase deficient-SCID
verfasst von
Alessandro Aiuti
Immacolata Brigida
Francesca Ferrua
Barbara Cappelli
Robert Chiesa
Sarah Marktel
Maria-Grazia Roncarolo
Publikationsdatum
01.07.2009
Verlag
Humana Press Inc
Erschienen in
Immunologic Research / Ausgabe 1-3/2009
Print ISSN: 0257-277X
Elektronische ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-009-8107-8

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