Complexities in comparing the impact of costimulatory domains on approved CD19 CAR functionality

Table 1 A summary of the architectures and manufacturing processes for the four approved anti-CD19 CARs, axicabtagene ciloleucel (axi-cel), brexucabtagene autoleucel (brexu-cel), tisagenlecleucel (tisa-cel) and lisocabtagene maraleucel (liso-cel)

	Axi-Cel	Brexu-Cel	Tisa-Cel	Liso-Cel
Architecture
Anti-CD19 scFv	FMC63	FMC63	FMC63	FMC63
Hinge	CD28	CD28	CD8α	IgG4
Transmembrane domain	CD28	CD28	CD8α	CD28
Costimulatory domain	CD28	CD28	4-1BB	4-1BB
Activation domain	CD3ζ	CD3ζ	CD3ζ	CD3ζ
Manufacturing
Viral vector	γ-Retrovirus	γ-Retrovirus	Lentivirus	Lentivirus
Promoter	MSCV	MSCV	EF1α	EF1α
Starting material	PBMCs	CD3 + enriched	CD3 + enriched	Separated CD4 and CD8
Activation	Anti-CD3 coated bag + IL2	Anti-CD3 and anti-CD28 coated bag + IL2	Expansion with beads coated with anti-CD3 and anti-CD28	Independent activation of CD4 and CD8 with beads coated with anti-CD3 and anti-CD28
CD4:CD8 in final product	Patient dependent	Patient dependent	Patient dependent	Defined CD4:CD8

ISSN: 1479-5876