Ex Vivo–expanded Natural Killer Cells Demonstrate Robust Proliferation In Vivo in High-risk Relapsed Multiple Myeloma Patients. Issue 1 (January 2015)

• Record Type: Journal Article
• Authors: Szmania, Susann; Lapteva, Natalia; Garg, Tarun; Greenway, Amy; Lingo, Joshuah; Nair, Bijay; Stone, Katie; Woods, Emily; Khan, Junaid; Stivers, Justin; Panozzo, Susan; Campana, Dario; Bellamy, William T.; Robbins, Molly; Epstein, Joshua; Yaccoby, Shmuel; Waheed, Sarah; Gee, Adrian; Cottler-Fox, Michele; Rooney, Cliona; Barlogie, Bart; van Rhee, Frits
• Is Part Of: Journal of immunotherapy. Volume 38:Issue 1(2015:Jan.)
• Publication Date: 2015-01
• Subjects: multiple myeloma -- natural killer cells -- immunotherapy; Immunotherapy -- Periodicals; Immunotherapy -- Periodicals; Neoplasms -- therapy -- Periodicals; Electronic journals; Electronic journals; 615.37
• DOI: 10.1097/CJI.0000000000000059
• Languages: English
• ISSNs: 1524-9557

Abstract

Abstract : Highly activated/expanded natural killer (NK) cells can be generated by stimulation with the human leukocyte antigen-deficient cell line K562, genetically modified to express 41BB-ligand and membrane-bound interleukin (IL)15. We tested the safety, persistence, and activity of expanded NK cells generated from myeloma patients (auto-NK) or haploidentical family donors (allo-NK) in heavily pretreated patients with high-risk relapsing myeloma. The preparative regimen comprised bortezomib only or bortezomib and immunosuppression with cyclophosphamide, dexamethasone, and fludarabine. NK cells were shipped overnight either cryopreserved or fresh. In 8 patients, up to 1×10 8 NK cells/kg were infused on day 0 and followed by daily administrations of IL2. Significant in vivo expansion was observed only in the 5 patients receiving fresh products, peaking at or near day 7, with the highest NK-cell counts in 2 subjects who received cells produced in a high concentration of IL2 (500 U/mL). Seven days after infusion, donor NK cells comprised >90% of circulating leukocytes in fresh allo-NK cell recipients, and cytolytic activity against allogeneic myeloma targets was retained in vitro. Among the 7 evaluable patients, there were no serious adverse events that could be related to NK-cell infusion. One patient had a partial response and in another the tempo of disease progression decreased; neither patient required further therapy for 6 months. In the 5 remaining patients, disease progression was not affected by NK-cell infusion. In conclusion, infusion of large numbers of expanded NK cells was feasible and safe; infusing fresh cells was critical to their expansion in vivo. Abstract : Supplemental Digital Content is available in the text.