Table 3.

Summary of Techniques to Overcome Checkpoint Blockade by CAR T Cells

Checkpoint Blockade in CAR T Cells	Mechanism	Reference
Anti-checkpoint antibody secretion	Blockade of PD-L1 on tumour cells	Suarez et al143
Anti-checkpoint scFv secretion	Blockade of PD-L1 on tumour cells	Zhou et al144 Li et al145 Rafiq et al146 Ping et al147
Dominant negative receptor	Expression of PD-1 receptor lacking intracellular domain outcompetes binding to PD-L1	Cherkassky et al148
Knockout of checkpoint receptors	Knock out of PD-1 by CRISPR/Cas9	Ren et al149 Rupp et al150 Choi et al151
Checkpoint receptor downregulation	Incorporation of shRNAs/siRNAs in CAR T cells for downregulation of PD-1/Tim-3/Lag-3/CTLA-4 expression	Cherkassky et al148 Liu et al152 Zou et al153 Simon et al154 Condomines et al155
Secretion of minibodies	Blockade of CTLA-4 on tumours	Yin et al156
Switch receptors	Conversion of PD-1 inhibitory signal to costimulatory or activating signal as in PD-1/CD28 switch receptor or PD-1 CARs	Liu et al157 Liu et al158 Parriott et al159