Polyvalent immunoglobulins, platelet lysate and lenalidomide: cocktail for polyfunctional NK cells expansion for multiple myeloma - Immunologie-Immunopathologie-Immunothérapie Accéder directement au contenu
Article Dans Une Revue Bone Marrow Transplantation Année : 2023

Polyvalent immunoglobulins, platelet lysate and lenalidomide: cocktail for polyfunctional NK cells expansion for multiple myeloma

Résumé

Despite the rapid development of new agents, myeloma (MM) continues to be an incurable disease. Growing bodies of literature suggest a key role of natural killer (NK) cells, a unique subset of CD3 − CD56 + innate lymphoid cells in the control of newly diagnosed MM. 1 MM cells promote a state of progressive immune dysregulation and suppression of NK cell functions, which support a growing interest for NK cell-based immunotherapy. 2 A major challenge to the broader application of adoptive NK cell therapy is to improve methods for in vitro expansion of low-frequency NK cells. Large-scale expansions have been obtained with various feeder cell-based systems but whereas these methods have merit, they also have major drawbacks including complicated procedures, safety issues for human administration and/or the expansion of exhausted NK cells. 3 Developing innovative strategies to generate clinically efficient NK cells with minimal in vitro manipulation, in large numbers, would provide an important breakthrough in NK cell-based immunotherapy. In the present studies, we report a strategy designed specifically for MM through expansion with polyvalent immunoglobulins (polyIgs) and platelet lysate (PL) in the presence of lenalidomide. NK cells were isolated from the non-mobilized apheresis product of 15 healthy donors who had given informed consent. The apheresis product started with 8.1 ± 4.4% NK cells. After depletion of CD3 + T cells and enrichment of CD56 + NK cells using the MACS selection system with CD3 and CD56 microbeads (Miltenyi Biotec GmbH, Bergisch Gladbach, Germany), the mean frequency of CD3 − CD56 + NK cells was 94.6 ± 1.9%, yielding an NK cell recovery of 35% with a mean T-cell depletion of 2.99 log. Freshly isolated CD3 − CD56 + cells were cultured in 24-well plates (Thermo Scientific Nunc A/S, Roskilde, Denmark) at a concentration of 0.5x10 6 cells/mL, in CellGro SCGM Medium good manufacturing practice (Cellgenix, Freiburg, Germany) containing 10 μg/mL ciprofloxacine (Bayer Santé, Puteaux, France) and 5 IU/ mL Fragmine (Pfizer, Paris, France). It was previously suggested that IL-2 predisposed NK cells to the activation of induced cell death, whereas IL-15 promoted NK cell development and survival. 4 In the present study, a median of 7.1 ± 0.7-fold NK cell expansion was obtained with IL-15 (Miltenyi Biotec, Bergisch Gladbach, Germany; 10 ng/mL) alone. In combination with IL-2 (Proleukin, Novartis Pharma, Rueil-Malmaison, France), NK cell growth increased significantly in a dose-dependent manner from 24.6 ± 2.5 (at 100 IU/mL) to 55.5 ± 6.0-fold (at 600 IU/mL) (P = 0.017) (Figure 1a, upper panel). Subsequently, cultures were performed in the presence of IL-15 (10 ng/mL) and IL-2 (600 IU/mL). Concomitantly, we tested NK cell expansion through coating. It has been suggested that anti-CD3 can potentiate the proliferation of NK cells through an indirect effect on T cells 2 or alternatively, we postulate the association of the Fc fragment with FcgRIII CD16, mainly expressed on mature NK cells. To test this hypothesis, we used human polyclonal immunoglobulins (PolyIgs; Tégéline, LFB Biomédicaments, Les Ulis, France
Fichier principal
Vignette du fichier
bmt2016311.pdf (408.11 Ko) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03992403 , version 1 (24-02-2023)

Identifiants

Citer

H Trébéden-Negre, V Vieillard, M Rosenzwajg, L Garderet, M Cherai, et al.. Polyvalent immunoglobulins, platelet lysate and lenalidomide: cocktail for polyfunctional NK cells expansion for multiple myeloma. Bone Marrow Transplantation, 2023, 52, pp.480 - 483. ⟨10.1038/bmt.2016.311⟩. ⟨hal-03992403⟩
27 Consultations
14 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More