Table 2 The comparison between the different famous types of CAR-armored immune cells. Cells like NK, NKT, and macrophage could be another alternative for T cells in a CAR-structure anti-cancer manner
From: The CAR macrophage cells, a novel generation of chimeric antigen-based approach against solid tumors
| Â | CAR-T | CAR-NK | CAR-NKT | CAR-Macrophage |
|---|---|---|---|---|
Intracellular signaling domain | CD3ζ  +  Costimulatory domains (CD28,4-1BB, CD137) | Like CAR T cells  +  NK-specific signaling domains (DAP10, DAP12, CD28,4-1BB,2B4) | Like CAR T cells + NK-receptors signaling domains + TCR-receptors signaling domains | Like CAR T cell +  ITAMs associated signaling domain +  Other ligands for modifying TME |
Transmembrane domain | CD8, CD28 | NKG2D, CD8, CD28 | CD8, CD28 | CD28, CD147, CD8 |
Source | Autologous or MHC-I matched allogeneic | Autologous / NK cell lines/ non-MHC-I allogeneic/PBMCs/UCB/ hPSCs/iPSCs/BM | PBMCs UCB hPSC/iPSCs | Autologous/ iPSCs/ hPSCs/Cell lines/BM/UCB/THP-1 cell line |
In-vitro expansion | Yes | In autologous: ok Cell lines: needed expansion before transduction | In autologous: ok Cell lines: needed expansion with α-GalCer-pulsed | In autologous: ok In iPSC and cell lines: required to expand before transduce |
Transduction efficacy | Higher | Low | Low | Low |
Cytokines are used for cell expansion | IL-2 | IL-15 | IL-2 | GM-CSF |
In-vivo controlling of proliferation and expansion (utilizing suicide genes) | Needed | Easier or not needed | Not be required commonly | Probably needed |
Repeat activation upon first antigen exposure | Slow | Fast | Fast | Fast |
Life span and persistence | High life span and long-term persistence | Low life span and limited persistency | Low life span and long-term persistency | Increased life span with limited persistency in circulation |
Repeat doses | Not needed | Needed | Needed | Not needed |
Tumor infiltration | Usually, poor | Usually, poor | Usually, poor | Very abundant |
Cytotoxicity effect | High | Low | High | High |
Cytotoxicity manner | CAR-dependent | Both CAR-dependent and CAR- independent | Cytotoxicity was dependent and independent of CAR The indirect anti-tumor function | Both CAR-dependent and mediated alteration of TME and mediate immunostimulatory TME and APC stimulate the immune response |
Cost | High | Low | Low | Low |
Off-the-shelf | Not significantly | Significant with cell lines With autologous cells possible while poor recovery or cryopreserve | Potential off-the-shelf CAR-cell products | Possible with a different source of macrophage |
Clinical outcomes | Proven with six FDA-approved drugs | Proven but without any approval therapy or drugs | Unproven but based on the clinical results, guess with significant action | Unproven but based on preclinical results guess with effective action |
Efficacy in solid tumors | low | Moderate | Moderate | High |
Side effect | Common and often with the fatality | Less common and usuriously risk | Less common and ungraciously risk | It is expected to be shared without clinical evidence with low fatality potential |