PMID- 29940772
OWN - NLM
STAT- MEDLINE
DCOM- 20190701
LR  - 20190701
IS  - 0028-2685 (Print)
IS  - 0028-2685 (Linking)
VI  - 65
IP  - 5
DP  - 2018 Sep 19
TI  - Carfilzomib combined with ex vivo-expanded patient autologous natural killer 
      cells for myeloma immunotherapy.
PG  - 720-729
LID - 171019N668 [pii]
LID - 10.4149/neo_2018_171019N668 [doi]
AB  - Natural killer (NK) cell-based immunotherapy is promising, as NK cells are in the 
      first line of defense against cancer and capital of lysing tumor cells without 
      pre-stimulation. However, NK cells from multiple myeloma (MM) patients are always 
      deficient in numbers and the expression of certain activating receptors, 
      disabling them in cytotoxicity against the cancer. Therefore, effective 
      strategies to expand NK cells and increase NK cell-mediated cytotoxicity against 
      MM are significant. Here, NK cells were efficiently expanded from peripheral 
      blood mononuclear cells (PBMCs) of newly diagnosed MM patients after co-culture 
      with irradiated K562 cells transfected with 41BBL and membrane-bound interleukin 
      (IL)-15 (K562-mb15-41BBL) in the presence of 200 IU/ml human IL-2. The ex 
      vivo-expanded NK cells were demonstrated to vigorously kill both MM cells and 
      autologous primary MM cells without significant lysis of patient normal cells. 
      Further exploration revealed a significant increase in cell surface expression of 
      most activating receptors of NK cells and indicated that expanded NK (exp-NK) 
      cell killing of MM cells was mediated by perforin/granzyme. NK cells are capital 
      of lysing human leukocyte antigen (HLA) I-deficient tumor cells and carfizomib, a 
      selective proteasome inhibitor approved for the treatment of relapsed/refractory 
      MM patient, down-regulates the expression of HLA class I, thus enhancing NK 
      cell-mediated lysis in MM. Here, we found for the first time that carfizomib 
      dramatically augmented ex vivo exp-NK cell cytotoxicity against patient 
      autologous MM cells, suggesting the use of exp-NK alone or in combination with 
      the drug to treat MM patient.
FAU - Chang, S K
AU  - Chang SK
AD  - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, China.
FAU - Hou, J
AU  - Hou J
AD  - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, China.
FAU - Chen, G G
AU  - Chen GG
AD  - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, China.
FAU - Yu, D D
AU  - Yu DD
AD  - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, China.
FAU - Wu, H Q
AU  - Wu HQ
AD  - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, China.
FAU - Xie, Y S
AU  - Xie YS
AD  - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, China.
FAU - Hu, L N
AU  - Hu LN
AD  - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, China.
FAU - Gao, L
AU  - Gao L
AD  - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, China.
FAU - Xiao, W Q
AU  - Xiao WQ
AD  - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, China.
FAU - Kong, Y Y
AU  - Kong YY
AD  - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, China.
FAU - Tao, Y
AU  - Tao Y
AD  - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, China.
FAU - Shi, J M
AU  - Shi JM
AD  - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University, 
      Shanghai, China.
AD  - Tongji University Cancer Center, Tongji University, Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20180618
PL  - Slovakia
TA  - Neoplasma
JT  - Neoplasma
JID - 0377266
RN  - 0 (Oligopeptides)
RN  - 72X6E3J5AR (carfilzomib)
SB  - IM
MH  - Cells, Cultured
MH  - Cytotoxicity, Immunologic
MH  - Humans
MH  - *Immunotherapy
MH  - K562 Cells
MH  - Killer Cells, Natural/*cytology
MH  - Leukocytes, Mononuclear
MH  - Multiple Myeloma/*therapy
MH  - Oligopeptides/*therapeutic use
MH  - Transfection
EDAT- 2018/06/27 06:00
MHDA- 2019/07/02 06:00
CRDT- 2018/06/27 06:00
PHST- 2017/10/19 00:00 [received]
PHST- 2018/02/28 00:00 [accepted]
PHST- 2018/06/27 06:00 [pubmed]
PHST- 2019/07/02 06:00 [medline]
PHST- 2018/06/27 06:00 [entrez]
AID - 171019N668 [pii]
AID - 10.4149/neo_2018_171019N668 [doi]
PST - ppublish
SO  - Neoplasma. 2018 Sep 19;65(5):720-729. doi: 10.4149/neo_2018_171019N668. Epub 2018 
      Jun 18.