Potential of NK cells in multiple Myeloma therapy

Khan, Abdullah; Devarakonda, Srinivas; Bumma, Naresh; Chaudhry, Maria; Benson, Don M.

doi:10.1080/17474086.2019.1617128

Cited by 15 publications

(11 citation statements)

References 121 publications

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“…Here, we discuss developments in T-cell-dependent immuno-oncology therapies in multiple myeloma, including vaccines, CPIs, cellular therapies, and bispecific antibodies (bsAb)/antibody constructs. MAbs (e.g., daratumumab, elotuzumab, and antibody drug conjugates) and NK cell-based therapies in multiple myeloma have been recently reviewed (23,24) and are beyond the scope of this review.…”

Section: T-cell-dependent Immuno-oncology Therapies In Multiple Myelomamentioning

confidence: 99%

How to Train Your T Cells: Overcoming Immune Dysfunction in Multiple Myeloma

Cohen

Raje

Fowler

et al. 2020

Clinical Cancer Research

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The progression of multiple myeloma, a hematologic malignancy characterized by unregulated plasma cell growth, is associated with increasing innate and adaptive immune system dysfunction, notably in the T-cell repertoire. Although treatment advances in multiple myeloma have led to deeper and more durable clinical responses, the disease remains incurable for most patients. Therapeutic strategies aimed at overcoming the immunosuppressive tumor microenvironment and activating the host immune system have recently shown promise in multiple myeloma, particularly in the relapsed and/or refractory disease setting. As the efficacy of T-cell-dependent immuno-oncology therapy is likely affected by the health of the endogenous T-cell repertoire, these therapies may also provide benefit in alternate treatment settings (e.g., precursor disease; after stem cell transplantation). This review describes T-cell-associated changes during the evolution of multiple myelo-ma and provides an overview of T-cell-dependent immunooncology approaches under investigation. Vaccine and checkpoint inhibitor interventions are being explored across the multiple myeloma disease continuum; treatment modalities that redirect patient T cells to elicit an anti-multiple myeloma response, namely, chimeric antigen receptor (CAR) T cells and bispecific antibodies [including BiTE (bispecific T-cell engager) molecules], have been primarily evaluated to date in the relapsed and/or refractory disease setting. CAR T cells and bispecific antibodies/antibody constructs directed against B-cell maturation antigen have generated excitement, with clinical data demonstrating deep responses. An increased understanding of the complex interplay between the immune system and multiple myeloma throughout the disease course will aid in maximizing the potential for T-cell-dependent immuno-oncology strategies in multiple myeloma.

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Section: T-cell-dependent Immuno-oncology Therapies In Multiple Myelomamentioning

confidence: 99%

How to Train Your T Cells: Overcoming Immune Dysfunction in Multiple Myeloma

Cohen

Raje

Fowler

et al. 2020

Clinical Cancer Research

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“…There are conflicting reports on the quantitative changes in NK cells although higher levels of circulating cytotoxic NK cells are seen in patients with long term disease control following stem cell transplant [38,55]. NK cell function can however be manipulated by malignant plasma cells and the surrounding TME.…”

Section: Nk-cell Dysregulation In Myelomamentioning

confidence: 99%

Shaping the Treatment Paradigm Based on the Current Understanding of the Pathobiology of Multiple Myeloma: An Overview

Ninkovic

Quach

2020

Cancers

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Multiple myeloma is an incurable malignancy which despite progressive improvements in overall survival over the last decade remains characterised by recurrent relapse with progressively shorter duration of response and treatment-free intervals with each subsequent treatment. Efforts to unravel the complex and heterogeneous genomic alterations, the marked dysregulation of the immune system and the multifarious interplay between malignant plasma cells and those of the tumour microenvironment have not only led to improved understanding of myelomagenesis and disease progression but have facilitated the rapid development of novel therapeutics including immunotherapies and small molecules bringing us a step closer to therapies that no doubt will extend survival. Novel therapeutic combinations both in the upfront and relapsed setting as well as novel methods to assess response and guide management are rapidly transforming the management of myeloma.

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“…Agents further along the path toward FDA approval are bb2121 (idecabtage vicleucel), 12 115 a second-generation CAR containing a 4-1BB costimulatory motif, which received Breakthrough Therapy designation in 2017, 116 and JNJ-68284528 (also called JNJ-4528, formerly LCAR-B38M), which binds to two distinct epitopes on BCMA, 117 118 and has also been granted Breakthrough Therapy designation in addition to PRIME designation by the European Medicines Agency (EMA). Additionally, under investigation are cell-based therapies using NK cells 119 as well as TCR-engineered T cells, such as the enhanced affinity NY-ESO-1 TCR. 120 …”

Section: Car T Cellsmentioning

confidence: 99%

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of multiple myeloma

Shah

Aiello

Avigan

et al. 2020

J Immunother Cancer

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Outcomes in multiple myeloma (MM) have improved dramatically in the last two decades with the advent of novel therapies including immunomodulatory agents (IMiDs), proteasome inhibitors and monoclonal antibodies. In recent years, immunotherapy for the treatment of MM has advanced rapidly, with the approval of new targeted agents and monoclonal antibodies directed against myeloma cell-surface antigens, as well as maturing data from late stage trials of chimeric antigen receptor CAR T cells. Therapies that engage the immune system to treat myeloma offer significant clinical benefits with durable responses and manageable toxicity profiles, however, the appropriate use of these immunotherapy agents can present unique challenges for practicing physicians. Therefore, the Society for Immunotherapy of Cancer convened an expert panel, which met to consider the current role of approved and emerging immunotherapy agents in MM and provide guidance to the oncology community by developing consensus recommendations. As immunotherapy evolves as a therapeutic option for the treatment of MM, these guidelines will be updated.

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Potential of NK cells in multiple Myeloma therapy

Cited by 15 publications

References 121 publications

How to Train Your T Cells: Overcoming Immune Dysfunction in Multiple Myeloma

How to Train Your T Cells: Overcoming Immune Dysfunction in Multiple Myeloma

Shaping the Treatment Paradigm Based on the Current Understanding of the Pathobiology of Multiple Myeloma: An Overview

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of multiple myeloma

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