Table 2.

Advantages and disadvantages of different sources to produce NK cells for immunotherapy

Source	Advantages	Disadvantages
Donor peripheral blood	Cells are mature; therefore, there is no need for lengthy differentiation protocols. Heterogeneity within the donor population allows for the selection of cells with favorable attributes such as KIR mismatch. Demonstrated clinical efficacy in treatment of AML.	Low frequency of NK cells in the peripheral blood limits the options for multiple dosing. Low efficiencies of transduction and transfection limits opportunities for genetic engineering. Variability between donors with respect to NK-cell function and proliferation.
Autologous peripheral blood	Lack of allo-reactivity could allow for longer persistence of cells after infusion. No need to go through the complex donor selection process.	No clinical benefit has been observed for autologous NK-cell adoptive transfer.
Cord blood CD34+ cells	Easier to engineer compared to peripheral blood NK cells. Large numbers of NK cells can be generated using in vitro differentiation protocols. Anti-CD19 CAR NK cells derived from cord blood CD34+ cells demonstrated clinical efficacy in the treatment of CLL.	Nonrenewable cell source with donor heterogeneity.
iPSCs	Unlimited renewal capability from well-characterized master cell banks. Precise multiplex engineering that only needs to be performed once per product derivation. Cells are generated from a single clone resulting in product homogeneity and consistency. Ability to generate large numbers of cells off-the-shelf for multiple patient doses.	Labor-intensive manufacturing process requires genetic engineering and cell culture expertise. Clinical testing is still in early stages.

CLL, chronic lymphocytic leukemia; KIR, killer immunoglobulin-like receptors.