Advances in gene therapy for inborn errors of immunity

LI Ting; SONG Hong-Mei

doi:10.7499/j.issn.1008-8830.2404027

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Chinese Journal of Contemporary Pediatrics ›› 2024, Vol. 26 ›› Issue (8) : 865-870. DOI: 10.7499/j.issn.1008-8830.2404027

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Advances in gene therapy for inborn errors of immunity

LI Ting, SONG Hong-Mei

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Abstract

Inborn errors of immunity (IEI) are a diverse group of disorders caused by defects in immune system structure or function, involving both innate and adaptive immunity. The 2022 update of the IEI classification includes 485 distinct disorders, categorized into ten major disease groups. With the rapid development of molecular biology, the specific pathogenesis of many IEI has been revealed, making gene therapy possible in preclinical and clinical research of this type of disease. This article reviews the advancements in gene therapy for IEI, aiming to increase awareness and understanding of these disorders.

Key words

Inborn error of immunity / Gene therapy / Severe combined immunodeficiency / Wiskott?Aldrich syndrome / Deficiency of adenosine deaminase 2

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LI Ting, SONG Hong-Mei. Advances in gene therapy for inborn errors of immunity[J]. Chinese Journal of Contemporary Pediatrics. 2024, 26(8): 865-870 https://doi.org/10.7499/j.issn.1008-8830.2404027

References

1 Castiello MC, Ferrari S, Villa A. Correcting inborn errors of immunity: from viral mediated gene addition to gene editing[J]. Semin Immunol, 2023, 66: 101731. PMID: 36863140. PMCID: PMC10109147. DOI: 10.1016/j.smim.2023.101731.
2 Arlabosse T, Booth C, Candotti F. Gene therapy for inborn errors of immunity[J]. J Allergy Clin Immunol Pract, 2023, 11(6): 1592-1601. PMID: 37084938. DOI: 10.1016/j.jaip.2023.04.001.
3 Pai SY, Logan BR, Griffith LM, et al. Transplantation outcomes for severe combined immunodeficiency, 2000-2009[J]. N Engl J Med, 2014, 371(5): 434-446. PMID: 25075835. PMCID: PMC4183064. DOI: 10.1056/NEJMoa1401177.
4 Tucci F, Galimberti S, Naldini L, et al. A systematic review and meta-analysis of gene therapy with hematopoietic stem and progenitor cells for monogenic disorders[J]. Nat Commun, 2022, 13(1): 1315. PMID: 35288539. PMCID: PMC8921234. DOI: 10.1038/s41467-022-28762-2.
5 Ott de Bruin LM, Lankester AC, Staal FJT. Advances in gene therapy for inborn errors of immunity[J]. Curr Opin Allergy Clin Immunol, 2023, 23(6): 467-477. PMID: 37846903. PMCID: PMC10621649. DOI: 10.1097/ACI.0000000000000952.
6 Friedmann T, Roblin R. Gene therapy for human genetic disease?[J]. Science, 1972, 175(4025): 949-955. PMID: 5061866. DOI: 10.1126/science.175.4025.949.
7 Blaese RM, Culver KW, Miller AD, et al. T lymphocyte-directed gene therapy for ADA- SCID: initial trial results after 4 years[J]. Science, 1995, 270(5235): 475-480. PMID: 7570001。 DOI: 10.1126/science.270.5235.475.
8 Ginn SL, Amaya AK, Alexander IE, et al. Gene therapy clinical trials worldwide to 2017: an update[J]. J Gene Med, 2018, 20(5): e3015. PMID: 29575374. DOI: 10.1002/jgm.3015.
9 Cring MR, Sheffield VC. Gene therapy and gene correction: targets, progress, and challenges for treating human diseases[J]. Gene Ther, 2022, 29(1-2): 3-12. PMID: 33037407. DOI: 10.1038/s41434-020-00197-8.
10 Tremblay JP, Annoni A, Suzuki M. Three decades of clinical gene therapy: from experimental technologies to viable treatments[J]. Mol Ther, 2021, 29(2): 411-412. PMID: 33472032. PMCID: PMC7854352. DOI: 10.1016/j.ymthe.2021.01.013.
11 Bulcha JT, Wang Y, Ma H, et al. Viral vector platforms within the gene therapy landscape[J]. Signal Transduct Target Ther, 2021, 6(1): 53. PMID: 33558455. PMCID: PMC7868676. DOI: 10.1038/s41392-021-00487-6.
12 Dogbey DM, Torres VES, Fajemisin E, et al. Technological advances in the use of viral and non-viral vectors for delivering genetic and non-genetic cargos for cancer therapy[J]. Drug Deliv Transl Res, 2023, 13(11): 2719-2738. PMID: 37301780. PMCID: PMC10257536. DOI: 10.1007/s13346-023-01362-3.
13 Kavanagh H, Dunne S, Martin DS, et al. A novel non-viral delivery method that enables efficient engineering of primary human T cells for ex vivo cell therapy applications[J]. Cytotherapy, 2021, 23(9): 852-860. PMID: 33941482. PMCID: PMC8386197. DOI: 10.1016/j.jcyt.2021.03.002.
14 Azarnezhad A, Samadian H, Jaymand M, et al. Toxicological profile of lipid-based nanostructures: are they considered as completely safe nanocarriers?[J]. Crit Rev Toxicol, 2020, 50(2): 148-176. PMID: 32053030. DOI: 10.1080/10408444.2020.1719974.
15 Gatti RA, Meuwissen HJ, Allen HD, et al. Immunological reconstitution of sex-linked lymphopenic immunological deficiency[J]. Lancet, 1968, 2(7583): 1366-9. PMID: 4177932. DOI: 10.1016/s0140-6736(68)92673-1.
16 Fischer A. Gene therapy for inborn errors of immunity: past, present and future[J]. Nat Rev Immunol, 2023, 23(6): 397-408. PMID: 36434109. DOI: 10.1038/s41577-022-00800-6.
17 Pai SY, Thrasher AJ. Gene therapy for X-linked severe combined immunodeficiency: historical outcomes and current status[J]. J Allergy Clin Immunol, 2020, 146(2): 258-261. PMID: 32561390. DOI: 10.1016/j.jaci.2020.05.055.
18 Aiuti A, Roncarolo MG, Naldini L. Gene therapy for ADA-SCID, the first marketing approval of an ex vivo gene therapy in Europe: paving the road for the next generation of advanced therapy medicinal products[J]. EMBO Mol Med, 2017, 9(6): 737-740. PMID: 28396566. PMCID: PMC5452047. DOI: 10.15252/emmm.201707573.
19 Tucci F, Scaramuzza S, Aiuti A, et al. Update on clinical ex vivo hematopoietic stem cell gene therapy for inherited monogenic diseases[J]. Mol Ther, 2021, 29(2): 489-504. PMID: 33221437. PMCID: PMC7854296. DOI: 10.1016/j.ymthe.2020.11.020.
20 Kohn DB, Booth C, Shaw KL, et al. Autologous ex vivo lentiviral gene therapy for adenosine deaminase deficiency[J]. N Engl J Med, 2021, 384(21): 2002-2013. PMID: 33974366. PMCID: PMC8240285. DOI: 10.1056/NEJMoa2027675.
21 Cowan MJ, Yu J, Facchino J, et al. Lentiviral gene therapy for Artemis-deficient SCID[J]. N Engl J Med, 2022, 387(25): 2344-2355. PMID: 36546626. PMCID: PMC9884487. DOI: 10.1056/NEJMoa2206575.
22 Garcia-Perez L, van Eggermond M, van Roon L, et al. Successful preclinical development of gene therapy for recombinase-activating gene-1-deficient SCID[J]. Mol Ther Methods Clin Dev, 2020, 17: 666-682. PMID: 32322605. PMCID: PMC7163047. DOI: 10.1016/j.omtm.2020.03.016.
23 Kohn LA, Kohn DB. Gene therapies for primary immune deficiencies[J]. Front Immunol, 2021, 12: 648951. PMID: 33717203. PMCID: PMC7946985. DOI: 10.3389/fimmu.2021.648951.
24 Ghanim HY, Porteus MH. Gene regulation in inborn errors of immunity: implications for gene therapy design and efficacy[J]. Immunol Rev, 2024, 322(1): 157-177. PMID: 38233996. DOI: 10.1111/imr.13305.
25 Albert MH, Slatter MA, Gennery AR, et al. Hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome: an EBMT inborn errors working party analysis[J]. Blood, 2022, 139(13): 2066-2079. PMID: 35100336. DOI: 10.1182/blood.2021014687.
26 Vieira RC, Pinho LG, Westerberg LS. Understanding immunoactinopathies: a decade of research on WAS gene defects[J]. Pediatr Allergy Immunol, 2023, 34(4): e13951. PMID: 37102395. DOI: 10.1111/pai.13951.
27 Braun CJ, Boztug K, Paruzynski A, et al. Gene therapy for Wiskott-Aldrich syndrome: long-term efficacy and genotoxicity[J]. Sci Transl Med, 2014, 6(227): 227ra33. PMID: 24622513. DOI: 10.1126/scitranslmed.3007280.
28 Aiuti A, Biasco L, Scaramuzza S, et al. Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome[J]. Science, 2013, 341(6148): 1233151. PMID: 23845947. PMCID: PMC4375961. DOI: 10.1126/science.1233151.
29 Labrosse R, Chu JI, Armant MA, et al. Outcomes of hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome[J]. Blood, 2023, 142(15): 1281-1296. PMID: 37478401. PMCID: PMC10731922. DOI: 10.1182/blood.2022019117.
30 Ferrua F, Marangoni F, Aiuti A, et al. Gene therapy for Wiskott-Aldrich syndrome: history, new vectors, future directions[J]. J Allergy Clin Immunol, 2020, 146(2): 262-265. PMID: 32623069. PMCID: PMC7453879. DOI: 10.1016/j.jaci.2020.06.018.
31 Cavazzana M, Thrasher A. Gene therapy for Whiskott-Aldrich syndrome: the latest news[J]. Clin Transl Med, 2022, 12(4): e815. PMID: 35437889. PMCID: PMC9016166. DOI: 10.1002/ctm2.815.
32 Laskowski TJ, Van Caeneghem Y, Pourebrahim R, et al. Gene correction of iPSCs from a Wiskott-Aldrich syndrome patient normalizes the lymphoid developmental and functional defects[J]. Stem Cell Reports, 2016, 7(2): 139-148. PMID: 27396937. PMCID: PMC4982969. DOI: 10.1016/j.stemcr.2016.06.003.
33 Rai R, Romito M, Rivers E, et al. Targeted gene correction of human hematopoietic stem cells for the treatment of Wiskott - Aldrich syndrome[J]. Nat Commun, 2020, 11(1): 4034. PMID: 32788576. PMCID: PMC7423939. DOI: 10.1038/s41467-020-17626-2.
34 Kohn DB, Booth C, Kang EM, et al. Lentiviral gene therapy for X-linked chronic granulomatous disease[J]. Nat Med, 2020, 26(2): 200-206. PMID: 31988463. PMCID: PMC7115833. DOI: 10.1038/s41591-019-0735-5.
35 Kohn DB, Rao GR, Almarza E, et al. A phase 1/2 study of lentiviral-mediated ex-vivo gene therapy for pediatric patients with severe leukocyte adhesion deficiency-I (LAD-I): results from phase 1[J]. Blood, 2020, 136, Supplement 1: 15. DOI: 10.1182/blood-2020-142484.
36 Borna S, Lee E, Sato Y, et al. Towards gene therapy for IPEX syndrome[J]. Eur J Immunol, 2022, 52(5): 705-716. PMID: 35355253. PMCID: PMC9322407. DOI: 10.1002/eji.202149210.
37 Lee PY, Aksentijevich I, Zhou Q. Mechanisms of vascular inflammation in deficiency of adenosine deaminase 2 (DADA2)[J]. Semin Immunopathol, 2022, 44(3): 269-280. PMID: 35178658. DOI: 10.1007/s00281-022-00918-8.
38 Lee PY, Davidson BA, Abraham RS, et al. Evaluation and management of deficiency of adenosine deaminase 2: an international consensus statement[J]. JAMA Netw Open, 2023, 6(5): e2315894. PMID: 37256629. DOI: 10.1001/jamanetworkopen.2023.15894.
39 Hashem H, Dimitrova D, Meyts I. Allogeneic hematopoietic cell transplantation for patients with deficiency of adenosine deaminase 2 (DADA2): approaches, obstacles and special considerations[J]. Front Immunol, 2022, 13: 932385. PMID: 35911698. PMCID: PMC9336546. DOI: 10.3389/fimmu.2022.932385.
40 Zoccolillo M, Brigida I, Barzaghi F, et al. Lentiviral correction of enzymatic activity restrains macrophage inflammation in adenosine deaminase 2 deficiency[J]. Blood Adv, 2021, 5(16): 3174-3187. PMID: 34424322. PMCID: PMC8405196. DOI: 10.1182/bloodadvances.2020003811.
41 Hong Y, Casimir M, Houghton BC, et al. Lentiviral mediated ADA2 gene transfer corrects the defects associated with deficiency of adenosine deaminase type 2[J]. Front Immunol, 2022, 13: 852830. PMID: 35529868. PMCID: PMC9073084. DOI: 10.3389/fimmu.2022.852830.
42 Vavassori V, Mercuri E, Marcovecchio GE, et al. Modeling, optimization, and comparable efficacy of T cell and hematopoietic stem cell gene editing for treating hyper-IgM syndrome[J]. EMBO Mol Med, 2021, 13(3): e13545. PMID: 33475257. PMCID: PMC7933961. DOI: 10.15252/emmm.202013545.