PMID- 35049413
OWN - NLM
STAT- MEDLINE
DCOM- 20220404
LR  - 20220531
IS  - 2164-554X (Electronic)
IS  - 2164-5515 (Print)
IS  - 2164-5515 (Linking)
VI  - 18
IP  - 1
DP  - 2022 Dec 31
TI  - IL-6/IFN-gamma double knockdown CAR-T cells reduce the release of multiple cytokines 
      from PBMCs in vitro.
PG  - 1-14
LID - 10.1080/21645515.2021.2016005 [doi]
AB  - CD19-targeted chimeric antigen receptor T (anti-CD19 CAR-T) cells have shown good 
      therapeutic results in the treatment of CD19 + B cell acute lymphocytic leukemia 
      and lymphoma. However, severe side reactions and cytotoxicity are great 
      challenges in the application of anti-CD19 CAR-T cell therapy. Cytokine release 
      syndrome (CRS) is the main side effect of CAR-T cell treatment, and interleukin-6 
      (IL-6) and interferon gamma (IFN-gamma) are cytokines that play major roles in CRS. 
      Therefore, we investigated double knockdown (KD) of IL-6 and IFN-gamma as a potential 
      strategy to manage anti-CD19 CAR-T cell-associated CRS. These improved anti-CD19 
      CAR-T cells therapy retained the advantages of the original anti-CD19 CAR-T cells 
      and additionally reduced the release of cytokines from CAR-T cells and other 
      immune cells. Moreover, this study presented a novel approach to abrogate CRS 
      through IL-6 and IFN-gamma KD, which may potentially inhibit the release of multiple 
      cytokines from CAR-T cells and peripheral blood mononuclear cells (PBMCs), a 
      model of CRS correlate with in vivo features of the CAR-T therapy, thereby 
      reducing the impact of CRS, improving the safety of CAR-T cell treatment, 
      reducing toxicities, and maintaining the function of CAR-T cells.
FAU - Zhang, Huihui
AU  - Zhang H
AD  - R&D Department, Qilu Cell Therapy Technology Co., Ltd, Jinan, Shandong, China.
FAU - Lv, Xiaofei
AU  - Lv X
AD  - Institute of Immunotherapy, Yinfeng Life Science Research Institute, Jinan, 
      Shandong, China.
FAU - Kong, Qunfang
AU  - Kong Q
AD  - R&D Department, Qilu Cell Therapy Technology Co., Ltd, Jinan, Shandong, China.
FAU - Tan, Yi
AU  - Tan Y
AUID- ORCID: 0000-0001-7310-9355
AD  - R&D Department, Qilu Cell Therapy Technology Co., Ltd, Jinan, Shandong, China.
AD  - Institute of Immunotherapy, Yinfeng Life Science Research Institute, Jinan, 
      Shandong, China.
LA  - eng
PT  - Journal Article
DEP - 20220120
PL  - United States
TA  - Hum Vaccin Immunother
JT  - Human vaccines & immunotherapeutics
JID - 101572652
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-6)
RN  - 0 (Receptors, Chimeric Antigen)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Cells, Cultured
MH  - Cytokine Release Syndrome/prevention & control
MH  - *Cytokines/metabolism
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Immunotherapy, Adoptive
MH  - *Interferon-gamma/genetics
MH  - *Interleukin-6/genetics
MH  - *Leukocytes, Mononuclear/metabolism
MH  - Receptors, Chimeric Antigen
MH  - *T-Lymphocytes/cytology
PMC - PMC8973323
OTO - NOTNLM
OT  - Chimeric antigen receptor
OT  - cytokine release syndrome
OT  - gene knockdown
OT  - interferon gamma
OT  - interleukin-6
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2022/01/21 06:00
MHDA- 2022/04/05 06:00
PMCR- 2022/01/20
CRDT- 2022/01/20 12:21
PHST- 2022/01/21 06:00 [pubmed]
PHST- 2022/04/05 06:00 [medline]
PHST- 2022/01/20 12:21 [entrez]
PHST- 2022/01/20 00:00 [pmc-release]
AID - 2016005 [pii]
AID - 10.1080/21645515.2021.2016005 [doi]
PST - ppublish
SO  - Hum Vaccin Immunother. 2022 Dec 31;18(1):1-14. doi: 
      10.1080/21645515.2021.2016005. Epub 2022 Jan 20.