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
| 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 |
Abbreviations: NK Natural killer, DAP DNAX activating protein, TCR T cell receptor, ITAM Immunoreceptor tyrosine-based activation motif, TME Tumor microenvironment, NKG2D Natural killer group 2 member D, MHC Major histocompatibility complex, PBMC Peripheral blood mononuclear cells, UCB Umbilical cord blood, hPSC Human pluripotent stem cells, iPSC Induced pluripotent stem cells, BM Bone marrow, IL Interleukin, GM-CSF Granulocyte–macrophage colony-stimulating factor, CAR Chimeric antigen receptor, APC Antigen-presenting cell, FDA Food and Drug Administration