Table 3 Comparison of CAR-T cells, CAR-NK cells, and CAR-macrophages in immunotherapy
Parameter | CAR-T cells | CAR-NK cells | CAR macrophage |
|---|---|---|---|
Cell source | Autologous or MHC-matched allogeneic T cells | Autologous, non-MHC-matched allogeneic NK cells or NK cell lines. Rich cell source | Autologous. Preclinical studies use iPSCs-derived macrophage and macrophage cell lines |
HD/MD | CD4, CD8a, CD28 | Similar to CAR-T structure, but can use NK-specific HD/TMD | Similar to CAR-T structure, but could use macrophage-specific HD/TMD |
ICD | CD3ζ plus a costimulatory domain, CD28, 4-1BB and others | Similar to the CAR-T structure, it can utilize NK-specific signaling domains like 2B4, DAP10, and DAP12 | Similar to the CAR-T structure, this design allows for the incorporation of alternative ITAM-containing signaling domains. Additional ligands can be employed, not for triggering phagocytosis, but rather to modify the tumor microenvironment |
CAR transduction | Primary T cells | Primary cells, iPSCs or cell lines | Primary cells, iPSCs or cell lines |
In vitro expansion | Yes | Yes for autologous NK cells. Cell line can be expanded after transduction and selection | Yes for autologous macrophages. iPSC and cell lines can beexpanded after transduction and selection |
Cytotoxicity mechanisms | CAR-dependent cell | Both CAR-dependent and CAR independent NK-cell natural cytotoxicity | CAR-dependent phagocytosis by macrophages, macrophage-driven immunostimulatory TIME, macrophage-induced tumor microenvironment alterations, and macrophages acting as antigenpresenting cells for immune response stimulation |
Cytokine release syndrome and neurotoxicity | Common and often serious | Less common and less serious | No clinical data |
Infiltration into TME | Typicall scare | Moderately common | Generally abundant |
Clinical experience or trial | Established effectiveness, with five FDA-approved CART therapies | o FDA-approved NK cell therapies yet. However, at least one trial has been published demonstrating a superior safety profile | No approved therapies, and limited clinical data is available |
Off-the-shelf CAR product | Unlikely. Usually autologous or MHC-matched allogeneic CAR-T cells | Yes with NK cell lines; potential with allogeneic NK cells, but poor recovery when cryopreserved | Theoretically possible with macrophage cell lines. However, there is no available clinical data |
Persistence | Can persist in the body, providing sustained effects | Typically have a shorter lifespan in the body. Memory-like NK cells | Their lifespan varies, and they can be influenced by the tissue |
Immunogenicity | Potential for cytokine release syndrome and neurotoxicity | Generally considered less immunogenic compared to CAR-T cells | Can modulate immune responses but may have limitations in terms of systemic use |
Clinical applicability | Primarily used in hematological malignancies | Maybe various cancers, especially in the context of allogeneic therapy. Maybe infectious disease | Different applicability |