Study‭ ‬of‭ ‬cord‭ ‬blood-derived‭ ‬natural‭ ‬killer‭ ‬cells combined‭ ‬with‭ ‬autologous‭ ‬stem‭ ‬cell‭ ‬transplantation‭ ‬in multiple‭ ‬myeloma

NK Cell and T Cells

NK Cell and T CellsT

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Summary

Multiple myeloma (MM) is a disease with known immune dysregulation, natural killer (NK) cells have shown preclinical activity in MM. A study was conducted to evaluate the effectiveness of Nk cells and the results demonstrated the safety and feasibility of allogeneic NK cells derived from umbilical cord blood and their potential role in myeloma immunotherapy. CB-NK immunotherapy were well tolerated and there were no cases of GVHD.

Introduction

The study involved 12 patients with symptomatic multiple myeloma aged 18-75 years old with adequate cardiac, hepatic, renal and pulmonary function.

The study aims to demonstrate for the first time, the safety and feasibility of allogeneic NK cells derived from umbilical cord blood and their potential role in myeloma immunotherapy.

Methodology

CB units were obtained from the MD Anderson Cord Blood Bank under an Institutional Review Board-approved protocol. On day −19, the CB unit was thawed, and mononuclear cells (MNCs) were isolated by Ficoll density gradient centrifugation. MNCs were cultured in a gas permeable bioreactor with irradiated (100 Gy) K562-based artificial antigen presenting cells (aAPCs) expressing membrane bound interleukin (IL) 21 “Clone 9.mbIL21, at a 2:1 aAPC:MNC ratio, and IL-2 (100 IU/mL). On day 7, cells were CD3-depleted immunomagnetically and the remaining cells were restimulated with the aAPC feeder cells and cultured for an additional 7 days.

On culture day 14, cells were harvested, and NK cell purity was determined by flow cytometry. The cells were then washed on the Sepax System and resuspended in 100 ml PlasmaLyte supplemented with 0.5% human serum albumin (HSA). An aliquot of the NK cell product was removed prior to infusion to assess the functional status of the CB-NK cells using intracellular flow cytometry [interferon (IFN)-y, TNF-a], and a standard chromium-51 (51Cr) assay with K562 erythroleukemia and MM cell lines RPMI 8226 and MM.1S as targets.

Treatment

Patients received lenalidomide (10mg orally daily) from days -8 and -2. Melphalan 200mg/m2 was given intravenously (IV) on day -7. The freshly expanded (1-5×108 cells per kg) CB-NK cells were infused on day -5.

Results

There were no toxicities with infusion of CB-NK cells.
Best response post-HCT, 2 patients achieved very good partial response (VGPR), 2 patients achieved near complete response (nCR), 4 patients exhibit stringent complete response (sCR), 2 patients achieved complete response (CR) and 2 patient had partial response (PR).

Conclusion

In this study, demonstrates for the first time, the safety and feasibility of allogeneic NK cells derived from umbilical cord blood and their potential role in myeloma immunotherapy. CB-NK immunotherapy were well tolerated and there were no cases of GVHD.

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Scientific article publishing date : 1/12/2016

Immucura identifier : BSC21_024EN

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