Paola Neri, Noémie Leblay, Holly Lee, Annamaria Gulla, Nizar J. Bahlis, Kenneth C. Anderson
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引用次数: 0
Abstract
A better understanding of the roles of the adaptive and innate immune systems in the oncogenesis of cancers including multiple myeloma (MM) has led to the development of novel immune-based therapies. B cell maturation antigen (BCMA), G protein-coupled receptor family C group 5 member D (GPRC5D) and Fc receptor-like protein 5 (FcRL5, also known as FcRH5) are cell-surface transmembrane proteins expressed by plasma cells, and have been identified as prominent immunotherapeutic targets in MM, with promising activity demonstrated in patients with heavily pretreated relapsed and/or refractory disease. Indeed, since 2020, antibody–drug conjugates, bispecific T cell engagers and autologous chimeric antigen receptor T cells targeting BCMA or GPRC5D have been approved for the treatment of relapsed and/or refractory MM. However, responses to these therapies are not universal, and acquired resistance invariably occurs. In this Review, we discuss the various immunotherapeutic approaches targeting BCMA, GPRC5D and FcRL5 that are currently either available or in clinical development for patients with MM. We also review the mechanisms underlying resistance to such therapies, and discuss potential strategies to overcome these mechanisms and improve patient outcomes. Novel immunotherapeutic strategies based on targeting specific tumour-associated antigens with antibody–drug conjugates (ADCs), chimeric antigen receptor (CAR) T cells and bispecific T cell engagers (BTEs) are revolutionizing the treatment of multiple myeloma. In this Review, the authors describe the clinical experience to date with ADCs, CAR T cells and BTEs targeting B cell maturation antigen, G protein-coupled receptor family C group 5 member D and Fc receptor-like protein 5. In addition, they discuss the mechanisms of resistance to such therapies, and potential strategies by which resistance could be overcome to improve patient outcomes.
期刊介绍:
Nature Reviews publishes clinical content authored by internationally renowned clinical academics and researchers, catering to readers in the medical sciences at postgraduate levels and beyond. Although targeted at practicing doctors, researchers, and academics within specific specialties, the aim is to ensure accessibility for readers across various medical disciplines. The journal features in-depth Reviews offering authoritative and current information, contextualizing topics within the history and development of a field. Perspectives, News & Views articles, and the Research Highlights section provide topical discussions, opinions, and filtered primary research from diverse medical journals.