Abstract
Peripheral T-cell lymphomas (PTCLs) are a group of very aggressive non- Hodgkin's lymphomas (NHLs) with poor prognoses and account for a majority of T-cell malignancies. Overall, the standard of care for patients with T-cell malignancies is poorly established, and there is an urgent clinical need for a new approach. As demonstrated in B-cell malignancies, chimeric antigen receptor (CAR) immunotherapy provides great hope as a curative treatment regimen. Because PTCLs develop from mature T-cells, these NHLs are commonly CD4+, and CD4 is highly and uniformly expressed. Therefore, CD4 is an ideal target for PTCL CAR immunotherapy. To that effect, we created a robust third-generation anti-CD4 CAR construct (CD4CAR) and introduced it into clonal NK cells (NK-92). CD4CAR NK-92 cells specifically and robustly eliminated diverse CD4+ human T-cell leukemia and lymphoma cell lines (KARPAS-299, CCRF-CEM, and HL60) and patient samples ex vivo. Furthermore, CD4CAR NK-92 cells effectively targeted KARPAS-299 cells in vivo that modeled difficult-to-access lymphoma nodules, significantly prolonging survival. In our study, we present novel targeting of CD4 using CAR-modified NK cells, and demonstrate efficacy. Combined, our data support CD4CAR NK cell immunotherapy as a potential new avenue for the treatment of PTCLs and CD4+ T-cell malignancies.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 112783-112796 |
| Number of pages | 14 |
| Journal | Oncotarget |
| Volume | 8 |
| Issue number | 68 |
| DOIs | |
| State | Published - Jan 1 2017 |
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Keywords
- Chimeric antigen receptors
- Immunotherapy
- NK cells
- T-cell malignancies
ASJC Scopus subject areas
- Oncology
Cite this
Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells. / Pinz, Kevin G.; Yakaboski, Elizabeth; Jares, Alexander; Liu, Hua; Firor, Amelia E.; Chen, Kevin H.; Wada, Masayuki; Salman, Huda Shafic; Tse, William; Hagag, Nabil; Lan, Fengshuo; Leung, Elaine Lai Han; Jiang, Xun; Ma, Yupo.
In: Oncotarget, Vol. 8, No. 68, 01.01.2017, p. 112783-112796.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells
AU - Pinz, Kevin G.
AU - Yakaboski, Elizabeth
AU - Jares, Alexander
AU - Liu, Hua
AU - Firor, Amelia E.
AU - Chen, Kevin H.
AU - Wada, Masayuki
AU - Salman, Huda Shafic
AU - Tse, William
AU - Hagag, Nabil
AU - Lan, Fengshuo
AU - Leung, Elaine Lai Han
AU - Jiang, Xun
AU - Ma, Yupo
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Peripheral T-cell lymphomas (PTCLs) are a group of very aggressive non- Hodgkin's lymphomas (NHLs) with poor prognoses and account for a majority of T-cell malignancies. Overall, the standard of care for patients with T-cell malignancies is poorly established, and there is an urgent clinical need for a new approach. As demonstrated in B-cell malignancies, chimeric antigen receptor (CAR) immunotherapy provides great hope as a curative treatment regimen. Because PTCLs develop from mature T-cells, these NHLs are commonly CD4+, and CD4 is highly and uniformly expressed. Therefore, CD4 is an ideal target for PTCL CAR immunotherapy. To that effect, we created a robust third-generation anti-CD4 CAR construct (CD4CAR) and introduced it into clonal NK cells (NK-92). CD4CAR NK-92 cells specifically and robustly eliminated diverse CD4+ human T-cell leukemia and lymphoma cell lines (KARPAS-299, CCRF-CEM, and HL60) and patient samples ex vivo. Furthermore, CD4CAR NK-92 cells effectively targeted KARPAS-299 cells in vivo that modeled difficult-to-access lymphoma nodules, significantly prolonging survival. In our study, we present novel targeting of CD4 using CAR-modified NK cells, and demonstrate efficacy. Combined, our data support CD4CAR NK cell immunotherapy as a potential new avenue for the treatment of PTCLs and CD4+ T-cell malignancies.
AB - Peripheral T-cell lymphomas (PTCLs) are a group of very aggressive non- Hodgkin's lymphomas (NHLs) with poor prognoses and account for a majority of T-cell malignancies. Overall, the standard of care for patients with T-cell malignancies is poorly established, and there is an urgent clinical need for a new approach. As demonstrated in B-cell malignancies, chimeric antigen receptor (CAR) immunotherapy provides great hope as a curative treatment regimen. Because PTCLs develop from mature T-cells, these NHLs are commonly CD4+, and CD4 is highly and uniformly expressed. Therefore, CD4 is an ideal target for PTCL CAR immunotherapy. To that effect, we created a robust third-generation anti-CD4 CAR construct (CD4CAR) and introduced it into clonal NK cells (NK-92). CD4CAR NK-92 cells specifically and robustly eliminated diverse CD4+ human T-cell leukemia and lymphoma cell lines (KARPAS-299, CCRF-CEM, and HL60) and patient samples ex vivo. Furthermore, CD4CAR NK-92 cells effectively targeted KARPAS-299 cells in vivo that modeled difficult-to-access lymphoma nodules, significantly prolonging survival. In our study, we present novel targeting of CD4 using CAR-modified NK cells, and demonstrate efficacy. Combined, our data support CD4CAR NK cell immunotherapy as a potential new avenue for the treatment of PTCLs and CD4+ T-cell malignancies.
KW - Chimeric antigen receptors
KW - Immunotherapy
KW - NK cells
KW - T-cell malignancies
UR - http://www.scopus.com/inward/record.url?scp=85038844700&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85038844700&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.22626
DO - 10.18632/oncotarget.22626
M3 - Article
VL - 8
SP - 112783
EP - 112796
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 68
ER -