Interim Results from an Ongoing Phase 1/2 Study of Lentiviral-mediated <i>Ex-vivo</i> Gene Therapy for Pediatric Patients with Severe Leukocyte Adhesion Deficiency-I (LAD-I)

Booth, Claire; Sevilla, Julián; Rao, Gayatri R.; Lopez, Maria Chitty; Almarza, Elena; Terrazas, Dayna; Zubicaray, Josune; Vicent, Marta González; Chetty, Kritika; O'Toole, Grainne; Xu‐Bayford, Jinhua; Nicoletti, Eileen; Fernandes, Augustine; Kuo, Caroline Y.; Oliveira, Satiro N. De; Moore, Theodore B.; Choi, Grace; Zeini, Miriam; Mesa-Núñez, Cristina; Thrasher, Adrian J.; Bueren, Juan A.; Schwartz, Jonathan D.; Kohn, Donald B.

doi:10.1182/blood-2022-158578

Cited by 1 publication

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“…However, initial trials using gRV vector were unsuccessful and terminated early as no corrected cells were detected [ 104 ]. Currently, trials are being conducted using LV vectors in combination with busulfan conditioning, with interim reports showing successful reversal of the LAD-1 phenotype [ 105 , 106 ].…”

Section: Gene Therapy For Other Iei Than Severe Combined Immunodefici...mentioning

confidence: 99%

Advances in gene therapy for inborn errors of immunity

Ott de Bruin,

Lankester,

Staal

2023

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of review Provide an overview of the landmark accomplishments and state of the art of gene therapy for inborn errors of immunity (IEI). Recent findings Three decades after the first clinical application of gene therapy for IEI, there is one market authorized product available, while for several others efficacy has been demonstrated or is currently being tested in ongoing clinical trials. Gene editing approaches using programmable nucleases are being explored preclinically and could be beneficial for genes requiring tightly regulated expression, gain-of-function mutations and dominant-negative mutations. Summary Gene therapy by modifying autologous hematopoietic stem cells (HSCs) offers an attractive alternative to allogeneic hematopoietic stem cell transplantation (HSCT), the current standard of care to treat severe IEI. This approach does not require availability of a suitable allogeneic donor and eliminates the risk of graft versus host disease (GvHD). Gene therapy can be attempted by using a viral vector to add a copy of the therapeutic gene (viral gene addition) or by using programmable nucleases (gene editing) to precisely correct mutations, disrupt a gene or introduce an entire copy of a gene at a specific locus. However, gene therapy comes with its own challenges such as safety, therapeutic effectiveness and access. For viral gene addition, a major safety concern is vector-related insertional mutagenesis, although this has been greatly reduced with the introduction of safer vectors. For gene editing, the risk of off-site mutagenesis is a main driver behind the ongoing search for modified nucleases. For both approaches, HSCs have to be manipulated ex vivo, and doing this efficiently without losing stemness remains a challenge, especially for gene editing.

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Section: Gene Therapy For Other Iei Than Severe Combined Immunodefici...mentioning

confidence: 99%