Abstract
Adoptive natural killer (NK) cell therapy may offer an effective treatment regimen for cancer patients whose disease is refractory to conventional therapy. NKcells can kill a wide range of tumor cells by patterned recognition of target ligands. We hypothesized that tumor targets sensitive to NK lysis would drive vigorous expansion of NK cells from human peripheral blood mononuclear cells (PBMC). Here, we provide the basis for developing a novel ex vivo expansion process. By screening class I-negative or -mismatched tumor cell lines we identified a Jurkat Tlymphoblast subline termed KL-1, which was highly effective in specifically expanding NK cells. KL-1 addition to PBMC cultures achieved approximately 100-fold expansion of NK cells with nearly 90% purity, accompanied by reciprocal inhibition of T-cell growth. Marked elevations in expression of activation receptors, natural cytotoxicity receptors (NKp30, NKp44), and adhesion molecules (CD11a, ICAM-1) were associated with high tumor-lytic capacity, in both in vitro and in vivo models. KL-1-mediated expansion of NK cells was contact dependent and required interactions with CD16, the Fcg receptor on NK cells, with ligands that are expressed on B cells. Indeed, B-cell depletion during culture abrogated selective NK cell expansion, while addition of EBV-transformed B cells further augmented NK expansion to approximately 740-fold. Together, our studies define a novel method for efficient activation of human NK cells that employs KL-1-lysed tumor cells and cocultured B cells, which drive a robust expansion of potent antitumor effector cells that will be useful for clinical evaluation.
| Original language | English |
|---|---|
| Pages (from-to) | 2598-2607 |
| Number of pages | 10 |
| Journal | Cancer Research |
| Volume | 73 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 2013 Apr 15 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Ex vivo expansion of highly cytotoxic human NK cells by cocultivation with irradiated tumor cells for adoptive immunotherapy. / Lim, Seon Ah; Kim, Tae Jin; Lee, Jung Eun; Sonn, Chung Hee; Kim, Kwanghee; Kim, Jiyoung; Choi, Jong Gwon; Choi, Il Kyu; Yun, Chae Ok; Kim, Jae-Hong; Yee, Cassian; Kumar, Vinay; Lee, Kyung-Mi.
In: Cancer Research, Vol. 73, No. 8, 15.04.2013, p. 2598-2607.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ex vivo expansion of highly cytotoxic human NK cells by cocultivation with irradiated tumor cells for adoptive immunotherapy
AU - Lim, Seon Ah
AU - Kim, Tae Jin
AU - Lee, Jung Eun
AU - Sonn, Chung Hee
AU - Kim, Kwanghee
AU - Kim, Jiyoung
AU - Choi, Jong Gwon
AU - Choi, Il Kyu
AU - Yun, Chae Ok
AU - Kim, Jae-Hong
AU - Yee, Cassian
AU - Kumar, Vinay
AU - Lee, Kyung-Mi
PY - 2013/4/15
Y1 - 2013/4/15
N2 - Adoptive natural killer (NK) cell therapy may offer an effective treatment regimen for cancer patients whose disease is refractory to conventional therapy. NKcells can kill a wide range of tumor cells by patterned recognition of target ligands. We hypothesized that tumor targets sensitive to NK lysis would drive vigorous expansion of NK cells from human peripheral blood mononuclear cells (PBMC). Here, we provide the basis for developing a novel ex vivo expansion process. By screening class I-negative or -mismatched tumor cell lines we identified a Jurkat Tlymphoblast subline termed KL-1, which was highly effective in specifically expanding NK cells. KL-1 addition to PBMC cultures achieved approximately 100-fold expansion of NK cells with nearly 90% purity, accompanied by reciprocal inhibition of T-cell growth. Marked elevations in expression of activation receptors, natural cytotoxicity receptors (NKp30, NKp44), and adhesion molecules (CD11a, ICAM-1) were associated with high tumor-lytic capacity, in both in vitro and in vivo models. KL-1-mediated expansion of NK cells was contact dependent and required interactions with CD16, the Fcg receptor on NK cells, with ligands that are expressed on B cells. Indeed, B-cell depletion during culture abrogated selective NK cell expansion, while addition of EBV-transformed B cells further augmented NK expansion to approximately 740-fold. Together, our studies define a novel method for efficient activation of human NK cells that employs KL-1-lysed tumor cells and cocultured B cells, which drive a robust expansion of potent antitumor effector cells that will be useful for clinical evaluation.
AB - Adoptive natural killer (NK) cell therapy may offer an effective treatment regimen for cancer patients whose disease is refractory to conventional therapy. NKcells can kill a wide range of tumor cells by patterned recognition of target ligands. We hypothesized that tumor targets sensitive to NK lysis would drive vigorous expansion of NK cells from human peripheral blood mononuclear cells (PBMC). Here, we provide the basis for developing a novel ex vivo expansion process. By screening class I-negative or -mismatched tumor cell lines we identified a Jurkat Tlymphoblast subline termed KL-1, which was highly effective in specifically expanding NK cells. KL-1 addition to PBMC cultures achieved approximately 100-fold expansion of NK cells with nearly 90% purity, accompanied by reciprocal inhibition of T-cell growth. Marked elevations in expression of activation receptors, natural cytotoxicity receptors (NKp30, NKp44), and adhesion molecules (CD11a, ICAM-1) were associated with high tumor-lytic capacity, in both in vitro and in vivo models. KL-1-mediated expansion of NK cells was contact dependent and required interactions with CD16, the Fcg receptor on NK cells, with ligands that are expressed on B cells. Indeed, B-cell depletion during culture abrogated selective NK cell expansion, while addition of EBV-transformed B cells further augmented NK expansion to approximately 740-fold. Together, our studies define a novel method for efficient activation of human NK cells that employs KL-1-lysed tumor cells and cocultured B cells, which drive a robust expansion of potent antitumor effector cells that will be useful for clinical evaluation.
UR - http://www.scopus.com/inward/record.url?scp=84876887378&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84876887378&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-12-2893
DO - 10.1158/0008-5472.CAN-12-2893
M3 - Article
C2 - 23580577
AN - SCOPUS:84876887378
VL - 73
SP - 2598
EP - 2607
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 8
ER -