Phase 1 clinical trial of adoptive immunotherapy using "off-the-shelf" activated natural killer cells in patients with refractory and relapsed acute myeloid leukemia

被引：142

作者：

Boyiadzis, Michael ^{[1
]}

Agha, Mounzer ^{[1
]}

Redner, Robert L. ^{[1
]}

Sehgal, Alison ^{[1
]}

Im, Annie ^{[1
]}

Hou, Jing-Zhou ^{[1
]}

Farah, Rafic ^{[1
]}

Dorritie, Kathleen A. ^{[1
]}

Raptis, Anastasios ^{[1
]}

Lim, Seah H. ^{[1
]}

Wang, Hong ^{[1
]}

Lapteva, Natalia ^{[2
,3
]}

Mei, Zhuyong ^{[2
,3
]}

Butterfield, Lisa H. ^{[1
]}

Rooney, Cliona M. ^{[2
,3
]}

Whiteside, Theresa L. ^{[1
]}

机构：

[1] Univ Pittsburgh, UPMC Hillman Canc Ctr, Pittsburgh, PA 15232 USA

[2] Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA

[3] Houston Methodist Hosp, Houston, TX USA

来源：

CYTOTHERAPY | 2017年 / 19卷 / 10期

关键词：

aNK cells; NK-92 cell line; acute myeloid leukemia; immune effects; immunotherapy; phase; 1; LINE NK-92; TRANSPLANTATION; CANCER; RECEPTORS; INFUSION;

D O I：

10.1016/j.jcyt.2017.07.008

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Background aims. Activated NK cells (aNK) generated by expansion of a human interleukin-2-dependent NK cell line (NK-92) were shown to mediate strong anti-leukemia activity. This phase 1 study evaluated feasibility, safety, and activity of aNK cells adoptively transferred to patients with refractory/relapsed acute myeloid leukemia (AML). In addition, effects of these aNK cells on the patient's immune system were evaluated. Methods. Two cell-dose levels (1 x 10(9) cells/m(2) and 3 x 10(9) cells/m(2)) were used. One treatment course consisted of two infusions of the same cell dose, each cell infusion delivered 24 h apart. The aNK cells were administered in the outpatient setting. Results. Seven patients with refractory/relapsed AML were treated with a total of 20 aNK cell infusions. None of the 7 patients experienced dose-limiting toxicities during the aNK cell administration or during 21 days of the post-infusion observation period. No grade 3-4 toxicities (probable or definite) related to aNK cell infusions occurred. Activity was transient in 3 of 7 patients. No significant changes in the patient's lymphocyte counts, subsets frequency, phenotype or activity were observed post-infusion. Cell dose-dependent effects in the plasma levels of several cytokines were observed. Discussion. The trial demonstrated the safety and feasibility of adoptive cell therapy with "off-the-shelf" aNK cells in patients with refractory/relapsed AML. These data provide the foundation for future combination immunotherapy trials and for the optimization of aNK cell based therapies in patients with AML.

引用

页码：1225 / 1232

页数：8

共 27 条

[1] Infusion of the allogeneic cell line NK-92 in patients with advanced renal cell cancer or melanoma: a phase I trial [J].

Arai, S. ;

Meagher, R. ;

Swearingen, M. ;

Myint, H. ;

Rich, E. ;

Martinson, J. ;

Klingemann, H. .

CYTOTHERAPY, 2008, 10 (06) :625-632

[2] Clearance of acute myeloid leukemia by haploidentical natural killer cells is improved using IL-2 diphtheria toxin fusion protein [J].

Bachanova, Veronika ;

Cooley, Sarah ;

Defor, Todd E. ;

Verneris, Michael R. ;

Zhang, Bin ;

McKenna, David H. ;

Curtsinger, Julie ;

Panoskaltsis-Mortari, Angela ;

Lewis, Dixie ;

Hippen, Keli ;

McGlave, Philip ;

Weisdorf, Daniel J. ;

Blazar, Bruce R. ;

Miller, Jeffrey S. .

BLOOD, 2014, 123 (25) :3855-3863

[3] Emerging insights into natural killer cells in human peripheral tissues [J].

Bjorkstrom, Niklas K. ;

Ljunggren, Hans-Gustaf ;

Michaelsson, Jakob .

NATURE REVIEWS IMMUNOLOGY, 2016, 16 (05) :310-320

[4]

BOYIADZIS M, 2016, BLOOD, V128

[5] Up-regulation of NK cell activating receptors following allogeneic hematopoietic stem cell transplantation under a lymphodepleting reduced intensity regimen is associated with elevated IL-15 levels [J].

Boyiadzis, Michael ;

Memon, Sarfraz ;

Carson, Jesse ;

Allen, Kenton ;

Szczepaski, Miroslaw R. ;

Vance, Barbara A. ;

Dean, Robert ;

Bishop, Michael R. ;

Gress, Ronald E. ;

Hakint, Frances T. .

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2008, 14 (03) :290-300

[6] Revised recommendations of the international working group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia [J].

Cheson, BD ;

Bennett, JM ;

Kopecky, KJ ;

Büchner, T ;

Willman, CL ;

Estey, EH ;

Schiffer, CA ;

Döhner, H ;

Tallman, MS ;

Lister, TA ;

LoCocco, F ;

Willemze, R ;

Biondi, A ;

Hiddemann, W ;

Larson, RA ;

Löwenberg, B ;

Sanz, MA ;

Head, DR ;

Ohno, R ;

Bloomfield, CD .

JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (24) :4642-4649

[7] Elevated serum interleukin-15 level in acute graft-versus-host disease after hematopoietic cell transplantation [J].

Chik, KW ;

Li, K ;

Pong, H ;

Shing, MMK ;

Li, CK ;

Yuen, PMP .

JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY, 2003, 25 (12) :960-964

[8] Therapeutic approaches to enhance natural killer cell cytotoxicity against cancer: the force awakens [J].

Childs, Richard W. ;

Carlsten, Mattias .

NATURE REVIEWS DRUG DISCOVERY, 2015, 14 (07) :487-498

[9] Defective expression and function of natural killer cell-triggering receptors in patients with acute myeloid leukemia [J].

Costello, RT ;

Sivori, S ;

Marcenaro, E ;

Lafage-Pochitaloff, M ;

Mozziconacci, MJ ;

Reviron, D ;

Gastaut, JA ;

Pende, D ;

Olive, D ;

Moretta, A .

BLOOD, 2002, 99 (10) :3661-3667

[10] Successful transfer of alloreactive haploidentical KIR ligand-mismatched natural killer cells after infusion in elderly high risk acute myeloid leukemia patients [J].

Curti, Antonio ;

Ruggeri, Loredana ;

D'Addio, Alessandra ;

Bontadini, Andrea ;

Dan, Elisa ;

Motta, Maria Rosa ;

Trabanelli, Sara ;

Giudice, Valeria ;

Urbani, Elena ;

Martinelli, Giovanni ;

Paolini, Stefania ;

Fruet, Fiorenza ;

Isidori, Alessandro ;

Parisi, Sarah ;

Bandini, Giuseppe ;

Baccarani, Michele ;

Velardi, Andrea ;

Lemoli, Roberto M. .

BLOOD, 2011, 118 (12) :3273-3279

← 1 2 3 →