INTRODUCTION Leukocyte adhesion deficiency type I (LAD-I) is a rare primary immunodeficiency caused by pathogenic variants of the ITGB2 gene, which encodes the β2 integrin subunit (CD18). Deficient CD18 expression on neutrophils impairs their migration to sites of infection, resulting in recurrent, severe infections that can be fatal if left untreated. The gene therapy marnetegragene autotemcel (marne-cel) aims to restore CD18 expression in myeloid cells by delivering a functional copy of the ITGB2 gene using a self-inactivating lentiviral vector. AREAS COVERED This article reviews the design of the marne-cel vector, its clinical administration protocol, and reported efficacy outcomes. It also examines safety considerations, including long-term follow-up monitoring with a focus on integration site analysis. Despite its clinical promise, the article highlights challenges related to the sustainable commercialization and broad accessibility of gene therapy. EXPERT OPINION Marne-cel represents a potentially curative treatment option for patients with severe LAD-I who lack a suitable matched donor. Clinical data demonstrate durable restoration of CD18 expression alongside a favorable safety profile. However, sustaining availability post-authorization remains a significant challenge due to high costs and logistical complexities. Ensuring equitable and long-term access will require systemic changes beyond pricing strategies, including sustained investment in global healthcare infrastructure.
INTRODUCTION House dust mites (HDMs) are the most prevalent inhalant allergens globally, inducing a spectrum of allergic diseases including allergic rhinitis (AR) and asthma, which substantially impair patients' quality of life. Sublingual immunotherapy (SLIT) is recognized as a promising disease-modifying intervention for HDM-related allergic disorders.Areas covered: This paper presents a narrative review of up-to-date clinical evidence regarding SLIT for HDM allergy (HDM-SLIT), covering its therapeutic efficacy, patient selection criteria, dose optimization strategies, safety profiles, underlying immunological mechanisms, and unresolved clinical challenges. EXPERT OPINION HDM-SLIT has been established as a disease-modifying therapy for HDM-induced AR and asthma, with supporting evidence demonstrating its clinical efficacy, favorable safety profile, and long-lasting tolerability. Future developments in precision allergology, including multiomics-derived biomarkers and digital health applications, show considerable potential to guide clinical decision-making. However, the translation of these advances into routine clinical practice remains limited by gaps in insurance reimbursement, suboptimal patient adherence, inconsistent regulatory standards across regions, insufficient product standardization, and inequitable access to healthcare resources.
