Table 1 CAR immune cell sources

CAR T-cell

Autologous

CAR T-cell

•Harvest T-cells from patients

•Low risk for GVHD

•Difficult to obtain a sufficient quantity of T-cells by apheresis in patients with T-cell malignancies or malignancies that receive chemotherapies

•Patients with rapidly progressing infections or cancers may not survive for several weeks needed to produce CAR T-cells

•Expensive

[28, 30]

Allogeneic

CAR T-cell

•Need for suitable donors

•Causes severe GVHD

•Allogeneic cells can be prepared and stored for future use so that there is a shorter waiting period vs. auto-CARs for infusion into the patient

•Expensive

[28, 29, 30]

CAR-NK cells

NK-92 cell line

•Easy to expand in vitro

•Source of limitless number of CAR-NK cells

•As the engineered NK-92 cells are of malignant origin, the cells must be irradiated. Irradiation shortens the survival of CAR-NK92 cells in the peripheral blood of the recipient

•They are naturally deprived of the CD16 domain, and are hence unable to trigger ADCC

[31, 32]

Peripheral blood mononuclear cells (PBMCs)

•Mature NK cells can be easily harvested

•Relatively few cells can be obtained from each donation

•90% of the NK cell population in PB unfortunately do not expand easily in vitro

•The cells obtained from PB respond more effectively and persist in circulation for longer than NKs from other sources

[32, 33, 34]

Umbilical cord blood (UCB)

•NK cells constitute about 30% of the lymphocytes in UCB

•Inferior cytotoxic capabilities compared to PB-derived NK cells

•Greater potential to expand than PB-derived NK cells

[34, 35]

Induced progenitor stem cells (iPSC)

•Harvest from the mobilized PB or from UCB

•The major virtue of iPSC-derived CAR-NK cells is the potential to produce large numbers of homogeneous CAR-NK cells from one iPSC

•This technology generates cells with an immature, less cytotoxic phenotype, similar to UCB-derived NK cells

[36, 37]