IL-2 activated NK cell immunotherapy of three children after haploidentical stem cell transplantation.
Natural killer (NK) cells are thought to be of benefit in HLA-mismatched hematopoietic transplantation (H-SCT). Therefore, we developed a protocol for clinical-use expansion of highly enriched and IL-2-stimulated NK cells. Purification of unstimulated leukaphereses by a two-step T cell depletion with a final CD56 enrichment procedure leads to a mean purity of 95% CD56(+)CD3- NK cells with a four- to five-log depletion of T cells. So far, three pediatric patients with multiply relapsed acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) were treated with repeated transfusions post-H-SCT. Directed killer immunoglobulin-like receptor (KIR) mismatches were demonstrated in all three cases. Although all patients showed blast persistence at the time of transplant, they reached complete remission and complete donor chimerism within 1 month post-H-SCT. NK cell therapy was tolerated well without graft-versus-host disease (GvHD) induction or other adverse events. The AML patient died of early relapse on day +80, while the ALL patients died of thrombotic-thrombocytopenic purpura and atypical viral pneumonia on days +45 and +152, respectively. This initial trial showed the feasibility of good manufacturing practice (GMP)-compliant NK cell isolation and expansion for clinical applications. We now launch a clinical phase I trial with activated NK cells post-H-SCT.
Koehl
Ulrike
U
University Hospital Frankfurt, Paediatric Haematology and Oncology, Frankfurt, Germany. koehl@em.uni-frankfurt.de
Sörensen
Jan
J
Esser
Ruth
R
Zimmermann
Stefanie
S
Grüttner
Hans Peter
HP
Tonn
Torsten
T
Seidl
Christian
C
Seifried
Erhard
E
Klingebiel
Thomas
T
Schwabe
Dirk
D
D000293:Adolescent; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002648:Child; D020544:Graft vs Leukemia Effect / Q000187:drug effects; D006239:Haplotypes; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods / Q000401:mortality; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000637:transplantation*; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000628:therapy*
D000970:Antineoplastic Agents; D007376:Interleukin-2