Table 4 The comparison of CAR-T cells with CAR-NK cells
From: NK cell upraise in the dark world of cancer stem cells
CAR-NK | CAR-T | |
|---|---|---|
Source | Various | Limited |
Expression of surface receptor (Ag-specific receptor) | Not required (germ line-encode) | Required (rearranged Ag-specific) |
Prior sensitization | Not required | Required |
Collection | Leukopheresis | Leukopheresis |
Preparation | Autologous: CD56+ Enrichment Allogeneic: MHC-matched donor selection or alloreactive T-cells depletion | Activation of cells with anti-CD3/CD28 beads Allogeneic donor: MHC match required |
Expansion | engineered feeders required (example: K562 cells expressing IL-15 and TNFSF9) plus IL-2 (in flasks, bags or bioreactors) | Flasks, bags or wave expansion system |
Transduction | Low transfection efficiency even with viral vectors | Desirable transfection efficacy Ex: Lentiviral systems transduce about 1/3 of T cells |
Cytotoxic mechanisms | Multiple receptors can trigger CAR-independent and FcR-dependent cytotoxicity | CAR-restricted killing In case of antigen loss on tumors, CAR-expressing T cells become ineffective |
Escaped tumor and infected cells recognition | Yes | No |
Clinical results | Proof of clinical benefit pending | Phase II studies have shown clinical benefit |
In vivo functionality | No need for suicide gene | Suicide genes are required to control life span in vivo |
HLA expression-related recognition | Dependent | Independent |
GVHD | Low/no | High/yes |
Cytokine-induced killer cells | No | Yes |
Toxicity | Low | High (neurotoxicity) |
Safety | High/low safe | Low/no safe |
Side effects | Limited life span in patients | “off target” effect prolonged Survival period in patient’s circulation CRS MQ activation syndrome Hemophagocytic Lymphohistiocytosis (hlh) |
Off-the-shelf availability | Present | Missing (preparation required for each patient) |
Cost | Cost benefit | Expensive |