Table 4.

The advantages and limitations of CAR- and NKR-engineered NK, NKT, and γδ T cells

Cell type	Advantages	Limitations
CAR- or NKR-NK	Tumor recognition: NKR, CD16, CAR; preventing tumor escape from antigen loss Potent cytotoxicity: synergistic cytotoxicity Reversing TME: eliminating MDSCs Safety: do not induce GVHD, low risk of CRS, no severe side effects Universal: Allogeneic “off-the-shelf” products	Limited persistence Low transduction efficiency
CAR-iNKT	Tumor recognition: dual targeting by CD1d and CAR; preventing tumor escape from antigen loss Potent cytotoxicity: synergistic cytotoxicity Tumor infiltration: Expression high levels of chemokine receptors → retain capacity of chemotaxis to tumor sites Reversing TME: eliminating TAMs Safety: Do not induce GVHD, limited off-target reactivity Universal: Allogeneic “off-the-shelf” products	Low numbers Limited persistence
CAR-γδ T	Tumor recognition: γδ TCR, NKR, CD16, CAR; preventing tumor escape from antigen loss Potent cytotoxicity: synergistic cytotoxicity APC function: acting as APCs to further promote antitumor effect of other immune cells (CD8+T cells) Tumor infiltration: high tropism to tumor sites Reversing TME: resistant to AICD and cell exhaustion Safety: low risk of GVHD, limited off-target reactivity Universal: Allogeneic “off-the-shelf” products	Low numbers Limited persistence Some subsets (e.g., IL-17+ γδ T cells) may have protumor effect