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 |