An evaluation of marnetegragene autotemcel for the treatment of severe leukocyte adhesion deficiency type I.

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.