Advantages and disadvantages of alternative immune effector cells as platforms for CAR engineering
| Alternative immune effector cell . | Advantages . | Disadvantages . | Safety profile . |
|---|---|---|---|
| NK cell | Multiple innate activating receptors that can mediate killing | Low persistence in the absence of cytokine | In early clinical results of CAR-NK cells: |
| Can harness KIR-ligand mismatch and “missing self” to reduce risk of relapse | Numerically few necessitating ex vivo expansion | -No GVHD | |
| Multiple mechanisms of cytotoxicity | Suboptimal trafficking and penetration into solid tumors | -No CRS | |
| No need for previous antigen priming | -No ICANS | ||
| Rapid tumor killing | |||
| iNKT | Innate and adaptive features | Can have immunosuppressive properties (Th2, Th17) | Limited clinical data with iNKT-CAR NK cells; reports in 2 patients showed no toxicity |
| Invariant TCR recognizes lipid antigens presented by CD1d | Numerically few requiring ex vivo expansion | In non–CAR-engineered cells: | |
| -No GVHD | |||
| -No toxicities | |||
| γδ T cells | Links innate and adaptive immune systems | Can have immunosuppressive properties (γδ T17, Vδ1 γδ T cells, γδ Treg) | No clinical data with CAR γδ T cells |
| MHC independent γδ TCR | Numerically few necessitating ex vivo expansion | In non–CAR-engineered cells: | |
| Cross-present antigens to αβ T cells | No GVHD | ||
| No toxicities | |||
| Macrophages | Good penetration into solid tumors | Can have immunosuppressive properties (M2) | No clinical data with CAR macrophages |
| Mediates phagocytosis and cytotoxicity | Numerically few necessitating ex vivo expansion | In non–CAR-engineered cells: | |
| Cross present antigens to αβ T cells | No GVHD | ||
| No toxicities | |||
| CIK | Multiple killing mechanisms including MHC-dependent and MHC-independent | Heterogeneous products | No clinical data with CAR CIK |
| Numerically few necessitating ex vivo expansion | In non–CAR-engineered cells: | ||
| Lower GVHD risk than T cells60 |
| Alternative immune effector cell . | Advantages . | Disadvantages . | Safety profile . |
|---|---|---|---|
| NK cell | Multiple innate activating receptors that can mediate killing | Low persistence in the absence of cytokine | In early clinical results of CAR-NK cells: |
| Can harness KIR-ligand mismatch and “missing self” to reduce risk of relapse | Numerically few necessitating ex vivo expansion | -No GVHD | |
| Multiple mechanisms of cytotoxicity | Suboptimal trafficking and penetration into solid tumors | -No CRS | |
| No need for previous antigen priming | -No ICANS | ||
| Rapid tumor killing | |||
| iNKT | Innate and adaptive features | Can have immunosuppressive properties (Th2, Th17) | Limited clinical data with iNKT-CAR NK cells; reports in 2 patients showed no toxicity |
| Invariant TCR recognizes lipid antigens presented by CD1d | Numerically few requiring ex vivo expansion | In non–CAR-engineered cells: | |
| -No GVHD | |||
| -No toxicities | |||
| γδ T cells | Links innate and adaptive immune systems | Can have immunosuppressive properties (γδ T17, Vδ1 γδ T cells, γδ Treg) | No clinical data with CAR γδ T cells |
| MHC independent γδ TCR | Numerically few necessitating ex vivo expansion | In non–CAR-engineered cells: | |
| Cross-present antigens to αβ T cells | No GVHD | ||
| No toxicities | |||
| Macrophages | Good penetration into solid tumors | Can have immunosuppressive properties (M2) | No clinical data with CAR macrophages |
| Mediates phagocytosis and cytotoxicity | Numerically few necessitating ex vivo expansion | In non–CAR-engineered cells: | |
| Cross present antigens to αβ T cells | No GVHD | ||
| No toxicities | |||
| CIK | Multiple killing mechanisms including MHC-dependent and MHC-independent | Heterogeneous products | No clinical data with CAR CIK |
| Numerically few necessitating ex vivo expansion | In non–CAR-engineered cells: | ||
| Lower GVHD risk than T cells60 |