Infusion of haplo-identical killer immunoglobulin-like receptor ligand mismatched NK cells for relapsed myeloma in the setting of autologous stem cell transplantation Journal Article
| Authors: | Shi, J.; Tricot, G.; Szmania, S.; Rosen, N.; Garg, T. K.; Malaviarachchi, P. A.; Moreno, A.; Dupont, B.; Hsu, K. C.; Baxter-Lowe, L. A.; Cottler-Fox, M.; Shaughnessy, J. D. Jr; Barlogie, B.; Van Rhee, F. |
| Article Title: | Infusion of haplo-identical killer immunoglobulin-like receptor ligand mismatched NK cells for relapsed myeloma in the setting of autologous stem cell transplantation |
| Abstract: | Killer immunoglobulin-like receptor (KIR)-ligand mismatched natural killer (NK) cells play a key role in achieving durable remission after haplo-identical transplantation for acute myeloid leukaemia. We investigated the feasibility of transfusing haplo-identical, T-cell depleted, KIR-ligand mismatched NK cells, after conditioning therapy with melphalan and fludarabine, to patients with advanced multiple myeloma (MM) followed by delayed rescue with autologous stem cells. No graft-versus-host disease or failure of autologous stem cells to engraft was observed. There was significant variation in the number of allo-reactive NK cells transfused. However, all NK products containing allo-reactive NK cells killed the NK cell target K562, the MM cell line U266, and recipient MM cells when available. Post NK cell infusion there was a rise in endogenous interleukin-15 accompanied by increasing donor chimaerism. Donor chimaerism was eventually lost, which correlated with the emergence of potent host anti-donor responses indicating that the immunosuppressive properties of the conditioning regimen require further optimization. Further, blocking of inhibitory KIR-ligands with anti-human leucocyte antigen antibody substantially enhanced killing of MM cells thus highlighting the potential for modulating NK/MM cell interaction. Encouragingly, 50% of patients achieved (near) complete remission. These data set the stage for future studies of KIR-ligand mismatched NK cell therapy in the autologous setting. © 2008 The Authors. |
| Keywords: | clinical article; controlled study; treatment outcome; unclassified drug; fludarabine; t lymphocyte; multiple myeloma; cell line; haplotypes; relapse; recurrence; dexamethasone; melphalan; autologous stem cell transplantation; hematopoietic stem cell transplantation; chimera; feasibility study; immunotherapy; remission; ligands; cell therapy; natural killer cell; killer cells, natural; receptors, kir; immunosuppressive treatment; cell interaction; transplantation, autologous; immunotherapy, adoptive; interleukin 15; alloimmunity; cytotoxicity tests, immunologic; immunoglobulin receptor; haplo-identical; killer immunoglobulin like receptor; leukocyte antibody |
| Journal Title: | British Journal of Haematology |
| Volume: | 143 |
| Issue: | 5 |
| ISSN: | 0007-1048 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2008-12-01 |
| Start Page: | 641 |
| End Page: | 653 |
| Language: | English |
| DOI: | 10.1111/j.1365-2141.2008.07340.x |
| PUBMED: | 18950462 |
| PROVIDER: | scopus |
| PMCID: | PMC3602915 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 21" - "Export Date: 17 November 2011" - "CODEN: BJHEA" - "Source: Scopus" |
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