Table 2.

Advantages and Disadvantages of Potential Cellular Sources for Allogeneic CARs.

Cell Type	Advantages	Disadvantages
NK cells (21, 23)	Intrinsic killing capability, lack of GVHD, decreased risk of off-target toxicity due to MHC-1 mediated regulation	Decreased persistence and tumor trafficking
iNKT cells (24–26)	Lack of GVHD, can kill via CAR and TCR, CNS activity	Unknown persistence, function may be impaired by lymphodepleting chemotherapy, possibly more challenging to isolate due to rarity of T cell population
γδ T cells (27–30)	Capable of MHC-independent killing, lack of GVHD	Unknown persistence, variable transduction efficacy, some subsets may be immunosuppressive
iPSC (31, 32)	Unlimited replication potential; can facilitate scaling up of cell engineering and customization of antigen specificity	May cause GVHD due to TCR; if TCR removed, persistence may be reduced due to NK cell-mediated destruction
EBV-CTL (33–35)	Specific targeting of virally driven DLBCL, minimal risk of GVHD	Unknown persistence, potential for off-target toxicity on other infected tissues that express EBV antigens
SCM/early memory T cells (36–38)	Potential for improved engraftment and expansion with less exhaustion due to less-differentiated phenotype	Unknown persistence and cytotoxicity relative to more differentiated T-cell subsets

CNS, central nervous system; EBV-CTL, Epstein Barr virus cytotoxic T cell; iNKT, invariant natural killer/T; iPSC, induced pluripotent stem cell; MHC, major histocompatibility complex; NK, natural killer; SCM, stem cell memory; TCR, T cell receptor.