Table 2 Advantages and disadvantages of different types of CAR-T cell therapy for allogeneic use (GvHD: graft-versus-host disease; iPSC: induced pluripotent stem cell; CIK: cytokine-induced killer)

Genetically modified αβ CAR-T cells

• Designed to be non-immunogenic

• High availability

• Additional steps of in vitro genetic manipulation

• Risk of off-target mutations

• Risk of GvHD due to residual TCRαβ⁺ T cells

• Low proliferation ex vivo

• High cost

[24, 25, 34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61]

γδ CAR-T cells

• HLA-independent antigen recognition (low risk of GvHD)

• NK receptor expression

• Cytotoxic phenotype

• Efficacy in solid tumours

• Short in vivo persistence

• Low availability

• Difficult ex vivo proliferation

[62,63,64,65,66,67,68,69,70]

iPSC CAR-T cells

• Unlimited source

• Homogeneous product (defined TCR specificity and HLA haplotype)

• Technically complex

• High cost

• Need of additional genetic modifications

• Additional quality controls to avoid undifferentiated iPSCs, which would compromise safety

[71,72,73,74,75,76,77]

Umbilical cord blood CAR-T cells

• Low risk of GvHD

• High proliferation capacity

• Limited number of cells

[78,79,80]

Central memory CAR-T cells

• Easy to obtain

• Low prone to develop GvHD (non-alloreactive TCR)

• Longer in vivo persistence than more differentiated T cells

• High percentage of effector memory T cells in the final product: lower in vivo persistence

[81,82,83]

Virus-specific CAR-T cells

• Viral TCR specificity (non-alloreactive TCR)

• Additional protection against viral infections

• Efficacy against virus-induced cancers

• Possibility of boosting in vivo via TCR stimulation

• Short in vivo persistence (but increases upon TCR stimulation with viral antigens)

[84,85,86,87,88,89,90,91]

CIK CAR-T cells

• Highly cytotoxic phenotype (NK-like)

• Minimal alloreactivity

• High cell heterogeneity

• Low proportion of early memory T cells: limited in vivo persistence

[92]