Xenograft model of childhood ALL
|
TCR-β-chain
|
RNP Electroporation
|
TCR- CAR T-cells
|
CD19
|
Retroviral
|
TCR knockout CAR-T cells are a promising option for tertiary patients
and showed no alloreactivity, despite their low persistency.
|
2020
(Stenger, Stief, Käuferle, et al., 2020)
|
Humanized murine model of glioma
|
TRAC, β2M, and PD-1
|
RNP Electroporation
|
Universal CAR-T cells resistant to PD-L1
|
EGFRvIII
|
AAV6 vector
|
CRISPR/Cas9 successfully generated universal CAR-T cells and enables
them to resist against PD-L1. This CAR T-cell showed prolong survival
and anti-tumor activity in mice.
|
2019
(Choi et al., 2019)
|
Humanized murine model of leukemia
|
TRAC
|
Cas9 mRNA Electroporation and gRNA lentiviral delivery
|
TCR- CAR T-cells
|
CD19
|
Lentiviral coupling CAR and gRNA
|
Separated delivery of CRISPR components may bring several advantages,
including time-saving and low immunogenicity. TCR-
CAR-T cells mediated highly effective leukemic eradication with less
evidence of exhaustion
|
2018
(Georgiadis et al., 2018)
|
Orthotopic mouse glioma model
|
PD-1
|
Plasmid
|
PD1-deficient CD133 CAR T-cells
|
CD133
|
PiggyBac transposon system
|
PD1-deficient CD133 CAR-T cells showed enhanced cytotoxicity and
proliferation but with cytokine secretion level. PD-1 destruction is
associated with higher antitumor responses.
|
2018
(B. Hu et al., 2019)
|
Mice with pre-B acute lymphoblastic leukemia
|
TRAC
|
Cas9 mRNA and gRNA Electroporation
|
TCR- CAR T-cells
|
CD19
|
AAV6 vector
|
Knocking out of TRAC locus led to CAR T-cell potency and delayed
effector CAR T differentiation and exhaustion.
|
2017
(Eyquem et al., 2017)
|
Xenograft tumor model of leukemia
|
PD-1
|
RNP
Electroporation
|
PD1-deficient CD19 CAR T-cells
|
CD19
|
Lentiviral
|
This study shed light on PD-1 inhibitory roles in CAR T-cells.
PD1-deficient CD19 CAR-T cells successfully eliminated tumor cells in
vivo.
|
2017
(Rupp et al., 2017)
|
Mice with B cell precursor leukemia (Nalm6 or Nalm6-PDL1 tumor
cells)
|
TCR, β2M, and PD1
|
Cas9 and gRNAs RNA Electroporation
|
Universal CAR-T cells resistant to PD-L1
|
PSCA and CD19
|
Lentiviral
|
TCR and β2M knockout CAR-T cells can be considered as universal CAR
T-cells. and PD1 knockout led to enhanced in vivo anti-tumor
activity.
|
2016
(Jiangtao Ren, Xiaojun Liu, et al., 2017)
|