Preclinical Evaluation of Invariant Natural Killer T Cells in the 5T33 Multiple Myeloma Model

Nur, Haneen; Fostier, Karel; Aspeslagh, Sandrine; Renmans, Wim; Bertrand, Elisabeth; Leleu, Xavier; Favreau, Mérédis; Breckpot, Karine; Schots, Rik; Waele, Marc De; Valckenborgh, Els Van; Bruyne, Elke De; Facon, Thierry; Elewaut, Dirk; Vanderkerken, Karin; Menu, Eline

doi:10.1371/journal.pone.0065075

Cited by 27 publications

(36 citation statements)

References 39 publications

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“…Engagement of CD1d (NKT ligand) also kills tumour cells in vitro [21], and NKT cells specific for an inflammationassociated lipid antigen, lysophosphatidylcholine, have been detected in patients with advanced myeloma [22]. Collectively, these findings indicate why a defective NKT cell pool may be associated with MM onset and relapse and support the concept that therapeutic targeting of NKT cells may be a useful strategy in treatment of MM in humans [12,13,16,17,19,23].…”

Section: Introductionmentioning

confidence: 68%

“…Earlier reports had indicated that NKT cell defects may be important in the development of MM [8,12,13,17,18] and that NKT cells could be a new target for immune-based treatment of MM patients [20,23]. To investigate the therapeutic significance of NKT cells in MM, we analysed NKT cell frequency and function in longitudinal studies of newly diagnosed patients with MM throughout several stages of therapy, with an emphasis on identifying and defining any NKT cell defects and determining the impact of lenalidomide treatment on NKT cell frequency and function.…”

Section: Discussionmentioning

confidence: 99%

“…Defective interferon (IFN)-γ production by NKT cells and a trend towards lower NKT cell frequencies reportedly affect patient groups with MM and are also observed in animal models of MM [8,12,17]. As a result, many studies have nominated NKT cells as a potential new target for treatment of MM in humans [12,13,16,[18][19][20].…”

Section: Introductionmentioning

confidence: 99%

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Natural killer T cell defects in multiple myeloma and the impact of lenalidomide therapy

Chan

Neeson

Leeansyah

et al. 2013

Clinical and Experimental Immunology

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SummaryThe causes of multiple myeloma (MM) remain obscure and there are few known risk factors; however, natural killer T (NKT) cell abnormalities have been reported in patients with MM, and therapeutic targeting of NKT cells is promoted as a potential treatment. We characterized NKT cell defects in treated and untreated patients with MM and determined the impact of lenalidomide therapy on the NKT cell pool. Lenalidomide is an immunomodulatory drug with co-stimulatory effects on NKT cells in vitro and is an approved treatment for MM, although its mode of action in that context is not well defined. We find that patients with relapsed/progressive MM had a marked deficiency in NKT cell numbers. In contrast, newly diagnosed patients had relatively normal NKT cell frequency and function prior to treatment, although a specific NKT cell deficiency emerged after high-dose melphalan and autologous stem cell transplantation (ASCT) regimen. This also impacted NK cells and conventional T cells, but the recovery of NKT cells was considerably delayed, resulting in a prolonged, treatment-induced NKT cell deficit. Longitudinal analysis of individual patients revealed that lenalidomide therapy had no in-vivo impact on NKT cell numbers or cytokine production, either as induction therapy, or as maintenance therapy following ASCT, indicating that its clinical benefits in this setting are independent of NKT cell modulation.

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Section: Introductionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

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Natural killer T cell defects in multiple myeloma and the impact of lenalidomide therapy

Chan

Neeson

Leeansyah

et al. 2013

Clinical and Experimental Immunology

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“…The agents include MK3475 (Pembrozilumab, Keytruda, by Merck & Co's) with pomalodomide (NCT02289222), with Len/Dex (NCT02036502), or post ASCT (NCT02331368), and the BMS-936558 (nivolumab, Bristol-Myers Squibb) NCT01592370 with other checkpoint inhibitors. (Qian et al, 2012;Freeman et al, 2011;Barber et al, 2011;Hofgaard et al, 2012;Nur et al, 2013 …”

Section: Pd-1/pd-l1mentioning

confidence: 99%

Immunotherapy for multiple myeloma: Current status and future directions

Ayed

Chang

Moreb

2015

Critical Reviews in Oncology/Hematology

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“…71,72 The monoclonal antibodies FRMF7 (elotuzumab) 42 and anti-CD38 (daratumumab, SAR650984), 66,73 particularly when associated with bortezomib/dexamethasone or lenalidomide/dexamethasone, may result in a relevant improvement. A newer exciting approach is immunotherapy with modified virus use, 74 natural killer cell therapy, 75,76 or chimeric antigen receptor strategies, 77 combining activity against malignant plasma cells and T-cell receptors. The above and other potential effective drugs in MM [78][79][80][81][82][83][84][85][86] are listed in Table 3.…”

Section: Future Directionsmentioning

confidence: 99%

How I treat relapsed myeloma

Bladé

Rosiñol

Larrea

2015

Blood

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Multiple myeloma (MM) is a plasma cell malignancy leading to significant life-expectancy shortening. Although the incorporation of the novel agents thalidomide, bortezomib, and lenalidomide in the front-line therapy has resulted in significant improvement, almost all patients relapse, making the treatment of relapse a real challenge. In the present article, when and how to treat relapsed MM is discussed. Treatment can be safely delayed in a subset of patients with asymptomatic relapse, whereas those with symptomatic relapse, advanced disease at diagnosis, or significant paraproteinemic increase require prompt rescue therapy. The benefit of retreatment and the use of a sequential approach for successive relapses considering drug synergism are highlighted. For patients with aggressive relapses and for those who have exhausted all available options, continued therapy until disease progression is recommended, particularly when using regimens with a long-term safety profile. Patients with a duration response to a first autologous stem cell transplantation (ASCT) longer than 2 years may benefit from a second ASCT. Patients with aggressive disease and/or poor cytogenetics at diagnosis relapsing within the first 2 years from ASCT should be considered for an allogeneic transplantation. Finally, a number of newer promising drugs are being actively investigated and the enrolment of patients in clinical trials is encouraged.

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Preclinical Evaluation of Invariant Natural Killer T Cells in the 5T33 Multiple Myeloma Model

Cited by 27 publications

References 39 publications

Natural killer T cell defects in multiple myeloma and the impact of lenalidomide therapy

Natural killer T cell defects in multiple myeloma and the impact of lenalidomide therapy

Immunotherapy for multiple myeloma: Current status and future directions

How I treat relapsed myeloma

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